@article {pmid42980393,
year = {2026},
author = {Liu, X and Zhang, Z and Fang, Y and Yuan, B and Lian, H and Yin, W and Zhang, J and Yuan, Q and Wang, S},
title = {Polygonatum cyrtonema Polysaccharide Ameliorates Functional Constipation in Mice via the Gut Microbiota-Pentadecanoic Acid-GPR40 Axis.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {43},
pages = {33918-33933},
doi = {10.1021/acs.jafc.6c06937},
pmid = {42980393},
issn = {1520-5118},
support = {0001/2025/TFP//Fundo para o Desenvolvimento das Ci?ncias e da Tecnologia/ ; 0002/2025/NRP//Fundo para o Desenvolvimento das Ci?ncias e da Tecnologia/ ; 0008/2025/EQP//Fundo para o Desenvolvimento das Ci?ncias e da Tecnologia/ ; 2023B1212120006//Guangdong-Hong Kong-Macau Joint Laboratory for Pharmacodynamic Constituents of TCM and New Drugs Research/ ; TP-001-2025//National Leading Talent Project Funding of China/ ; },
mesh = {Animals ; Mice ; *Polysaccharides/administration & dosage ; *Gastrointestinal Microbiome/drug effects ; *Constipation/drug therapy/microbiology/metabolism/physiopathology/genetics ; Male ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Humans ; *Polygonatum/chemistry ; Bacteria/isolation & purification/classification/genetics/metabolism ; Mice, Inbred C57BL ; *Plant Extracts/administration & dosage ; },
abstract = {Constipation is a widespread gastrointestinal dysfunction that severely diminishes life satisfaction, yet current pharmacological interventions frequently carry risks of dependency. This study investigates the therapeutic potential and underlying mechanism ofPolygonatum cyrtonema polysaccharide (PCP), an inulin neoseries-type fructan, in mitigating loperamide-induced constipation in mice. Our results demonstrated that PCP treatment significantly normalized defecation indicators, including increased fecal water content and accelerated small-intestinal transit. Fecal microbiota transplantation (FMT) confirmed that the anti-constipation efficacy of PCP was driven by the gut microbiota. Integrated 16S rRNA sequencing and metabolomic profiling revealed that PCP remodeled the gut microbiota, particularly enriching Lachnospiraceae, which subsequently drove the accumulation of pentadecanoic acid (PDA). Mechanistically, PDA served as a key microbial metabolite that enhanced colonic motility, likely by activating the GPR40 receptor. These findings identify the "PCP-microbiota-PDA-GPR40" axis as an novel pathway for alleviating functional constipation, supporting PCP as a promising prebiotic candidate or functional food ingredient.},
}

Animals
Mice
*Polysaccharides/administration & dosage
*Gastrointestinal Microbiome/drug effects
*Constipation/drug therapy/microbiology/metabolism/physiopathology/genetics
Male
*Receptors, G-Protein-Coupled/metabolism/genetics
Humans
*Polygonatum/chemistry
Bacteria/isolation & purification/classification/genetics/metabolism
Mice, Inbred C57BL
*Plant Extracts/administration & dosage

@article {pmid42980459,
year = {2026},
author = {Zhou, Z and Fang, Y and Luo, M and Du, H and Guo, X and Chen, Y and Han, Y and Xiao, H},
title = {Gut Microbiota-Mediated Liberation of Ellagic Acid from Strawberry Soluble Fiber and Its Metabolism: In Vitro and In Vivo Evidence.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {43},
pages = {34126-34136},
doi = {10.1021/acs.jafc.6c07831},
pmid = {42980459},
issn = {1520-5118},
support = {2019-67017-29249//National Institute of Food and Agriculture/ ; 2020-67017-30835//National Institute of Food and Agriculture/ ; 2020-67017-30844//National Institute of Food and Agriculture/ ; 2023-67017-40248//National Institute of Food and Agriculture/ ; 2026-67021-45661//National Institute of Food and Agriculture/ ; 3060-21650-002-057-S//Agricultural Research Service/ ; },
mesh = {*Ellagic Acid/metabolism/chemistry ; *Dietary Fiber/metabolism/analysis ; *Fragaria/metabolism/chemistry ; Animals ; Humans ; Mice ; *Gastrointestinal Microbiome ; Feces/microbiology ; *Bacteria/metabolism/isolation & purification/genetics/classification ; Fruit/metabolism/chemistry ; Fermentation ; Male ; Coumarins/metabolism ; Hydrolyzable Tannins ; },
abstract = {This study investigated strawberry soluble fiber (SSF) as a reservoir of celobiotics and evaluated their microbial liberation and metabolism both in vitro and in vivo. In vitro colonic fermentation of SSF combined with untargeted metabolomics identified urolithin C/iso-urolithin C, a gut microbial metabolite derived exclusively from ellagic acid (EA), suggesting the microbial liberation of matrix-embedded EA from SSF. This hypothesis was validated by pectinase treatment, which increased total EA equivalents by approximately 10-fold. Time-course fermentation demonstrated rapid EA liberation from SSF and its subsequent urolithin conversion, which was further confirmed in human-microbiota-transplanted mice after SSF consumption in vivo. Notably, substantial interindividual variation was observed in the capacities of human fecal microbiota to release EAs and produce urolithins. Beyond SSF, EA is widely distributed among plant-derived dietary fibers (DFs) and is particularly abundant in berry fibers. This work expanded the celobiotic concept and highlighted the importance of the microbiota-mediated release of hidden phytochemicals from dietary fibers.},
}

*Ellagic Acid/metabolism/chemistry
*Dietary Fiber/metabolism/analysis
*Fragaria/metabolism/chemistry
Animals
Humans
Mice
*Gastrointestinal Microbiome
Feces/microbiology
*Bacteria/metabolism/isolation & purification/genetics/classification
Fruit/metabolism/chemistry
Fermentation
Male
Coumarins/metabolism
Hydrolyzable Tannins

@article {pmid42982582,
year = {2026},
author = {Wang, K and Liu, Y and Wang, L and Xu, Y and Gu, Z and Sun, R and Wei, C and Zhao, Q and Li, B and Yan, X and Qiu, Y},
title = {Chronic Arsenic Exposure Induces Hepatocyte Proliferation in Rats via the Gut-Liver Axis: Interventions With Fecal Microbiota Transplantation and/or Arsenic Withdrawal.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.70494},
pmid = {42982582},
issn = {1099-1263},
support = {20250022//Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province/ ; //Shanxi Province Higher Education "Billion Project" Science/ ; TMSYSKF2025002//Technology Guidance Project and Open Project of Key Laboratory of Neurological Disease Prevention and Research of Shanxi Province/ ; },
abstract = {Arsenic (As) contamination in groundwater has been reported in many countries and is a major risk factor for liver injury. While the impact of arsenic exposure on gut microbiota and its role in liver diseases through the gut-liver axis has been documented, the underlying mechanism remains unclear. In this study, we established a chronic arsenic exposure rat model by administering sodium arsenite (NaAsO2) at concentrations of 30 and 100 mg/L through drinking water until 62 weeks of age. Subsequently, high As-exposed rats were subjected to fecal microbiota transplantation (FMT), arsenic cessation, or combined FMT and arsenic cessation interventions for 2 months. Liver pathological changes, hepatocyte proliferation, intestinal microbiota composition, fecal butyrate levels, and the expression of butyrate-related molecular markers were evaluated using hematoxylin-eosin staining, immunohistochemistry, 16S rRNA gene sequencing, gas chromatography, and quantitative real-time PCR. Chronic arsenic exposure increased hepatocyte proliferation, as evidenced by elevated PCNA and Ki-67 expression in liver tissues. Microbiota analysis revealed that arsenic exposure significantly altered gut microbial community structure and reduced the abundance of butyrate-producing bacteria, particularly Lachnospiraceae and Blautia. Consistently, fecal butyrate levels showed a decreasing trend after arsenic exposure. Furthermore, arsenic exposure significantly suppressed hepatic miR-22 expression, accompanied by increased expression of Sirt1 and Ctnnb1 and decreased expression of Gsk3b, suggesting activation of a proliferation-related signaling pathway. Intervention with FMT and/or arsenic cessation partially restored gut microbiota composition, alleviated miR-22 suppression, and improved arsenic-induced molecular alterations. Collectively, these findings demonstrate that chronic arsenic exposure promotes hepatocyte proliferation through disruption of gut microbiota and reduction of microbiota-derived butyrate, which may regulate the miR-22/Sirt1 signaling pathway. Restoration of intestinal microbiota by FMT or cessation of arsenic exposure may provide potential strategies for mitigating arsenic-induced hepatic abnormalities.},
}

@article {pmid42982767,
year = {2026},
author = {Passannante, M and Laudisi, A and Ghiso, A and Francia, G and Di Grazia, C and Dominietto, A and Bregante, S and Varaldo, R and Gambella, M and Angelucci, E and Raiola, AM},
title = {Managing acute graft-versus-host disease after allogeneic stem cell transplantation.},
journal = {Expert review of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1080/17474086.2026.2760637},
pmid = {42982767},
issn = {1747-4094},
abstract = {INTRODUCTION: Acute graft-versus-host disease (aGVHD) remains a leading cause of morbidity and non-relapse mortality after allogeneic hematopoietic cell transplantation. Despite progress in prophylactic strategies, its management remains challenging: corticosteroids are still the mainstay of first-line care, yet a substantial proportion of patients fail to achieve durable responses, underscoring the need for more effective and less toxic alternatives.

AREAS COVERED: This review outlines the current approach to aGVHD, from first-line management to steroid-refractory disease and beyond. It covers corticosteroid optimization, the established role of ruxolitinib in the steroid-refractory setting, and the use of extracorporeal photopheresis in selected patients. Cellular, microbiome-based, cytokine-directed, and regenerative strategies acting on complementary pathogenic mechanisms are also discussed. The literature was identified through a PubMed search using the terms 'acute graft-versus-host disease' and 'treatment,' including publications up to 30 June 2026, supplemented by manual screening of reference lists.

EXPERT OPINION: Ruxolitinib has reshaped the management of steroid-refractory aGVHD, although important unmet needs persist. Future progress will depend not only on new agents but on smarter use of existing options: minimizing steroid exposure, refining sequencing, and integrating combinations earlier. Biomarker-guided risk stratification may ultimately support a more individualized approach, improving disease control while limiting toxicity.},
}

@article {pmid42982830,
year = {2026},
author = {Song, Y and Xu, J and Zhao, J and Yang, R and Ma, Y and Hou, YM and Cao, Y and Li, J and Yu, S and Liang, X and Zhang, Y and Wang, K and An, L and Liu, Y and Meng, ZX and Fan, JG and Xie, C},
title = {Neonatal overfeeding accelerates age-related sarcopenia and metabolic disorders through lifelong gut mucosa and microbiota programming in mice.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42982830},
issn = {2041-1723},
support = {82530024//National Natural Science Foundation of China (National Science Foundation of China)/ ; 92557304//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82570954//National Natural Science Foundation of China (National Science Foundation of China)/ ; 92457301//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Animals ; *Sarcopenia/microbiology/metabolism/etiology/pathology ; Mice ; Female ; *Aging/metabolism ; *Intestinal Mucosa/metabolism/microbiology ; Animals, Newborn ; Male ; *Gastrointestinal Microbiome/physiology ; *Overnutrition/complications ; Fecal Microbiota Transplantation ; *Metabolic Diseases/metabolism/microbiology/etiology ; Mice, Inbred C57BL ; Muscle, Skeletal/metabolism/pathology ; Dysbiosis ; Disease Models, Animal ; Akkermansia ; },
abstract = {Early-life nutrition shapes lifelong health, yet the long-term consequences of childhood overnutrition, particularly on musculoskeletal aging, remain unclear. Here, we show that neonatal overfeeding acts as a developmental insult that accelerates age-related sarcopenia in both sexes. Using different mouse models, early overnutrition shortens lifespan and exacerbates late-life muscle atrophy, accompanied by metabolic dysfunction. Mechanistically, neonatal overfeeding disrupts goblet cell development, leading to persistent mucus barrier defects and consequently reduced Akkermansia muciniphila (A. muciniphila) colonization during aging. Fecal microbiota transplantation transfers the sarcopenic phenotype, implicating gut dysbiosis in disease propagation. Loss of A. muciniphila reduces acetate production, impairs muscle mitochondrial function at least in part via suppressed GPR43 signaling, and aggravates sarcopenia. Conversely, A. muciniphila reconstitution or acetate supplementation restores mitochondrial homeostasis and improves muscle performance in aged mice. These findings reveal a developmental origin of age-related sarcopenia and define a gut-muscle axis linking early-life overnutrition to muscle aging, highlighting the preventive potential of optimizing early nutrition to support healthy aging.},
}

Animals
*Sarcopenia/microbiology/metabolism/etiology/pathology
Mice
Female
*Aging/metabolism
*Intestinal Mucosa/metabolism/microbiology
Animals, Newborn
Male
*Gastrointestinal Microbiome/physiology
*Overnutrition/complications
Fecal Microbiota Transplantation
*Metabolic Diseases/metabolism/microbiology/etiology
Mice, Inbred C57BL
Muscle, Skeletal/metabolism/pathology
Dysbiosis
Disease Models, Animal
Akkermansia

@article {pmid42982861,
year = {2026},
author = {Pomej, K and Frick, A and Scheiner, B and Baumgartner, M and Schmetterer, KG and Reyna-Blanco, CS and Balcar, L and Pajancic, L and Kreuter, A and Séneca, J and Hausmann, B and Köcher, T and Prinzensteiner, M and Lampichler, K and Rohr-Udilova, N and Chakrabarty, A and Klotz, A and Lampl, AC and Zinober, K and Regnat, K and Trauner, M and Berry, D and Tamandl, D and Vogl, T and Gasche, C and Pinter, M},
title = {FMT combined with atezolizumab-bevacizumab in hepatocellular carcinoma refractory to immunotherapy: an open label, single-arm, phase II pilot study.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42982861},
issn = {2041-1723},
mesh = {Humans ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage/adverse effects ; *Liver Neoplasms/therapy/immunology/mortality ; Pilot Projects ; *Bevacizumab/therapeutic use/administration & dosage/adverse effects ; *Carcinoma, Hepatocellular/therapy/immunology/mortality ; Female ; Male ; Middle Aged ; *Fecal Microbiota Transplantation/methods/adverse effects ; Aged ; Immunotherapy/methods ; Combined Modality Therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Combined Antibody Therapeutics ; },
abstract = {Fecal microbiota transplantation (FMT) may help to overcome resistance to immunotherapy. In this single-center, single-arm phase II hypothesis-generating pilot study (FAB-HCC), we included 12 patients with advanced hepatocellular carcinoma (HCC) who progressed on atezolizumab plus bevacizumab. Patients received a single FMT via colonoscopy from a donor with HCC who responded to anti-PD-1 treatment or a healthy donor, combined with atezolizumab plus bevacizumab. The primary endpoint was safety as measured by incidence and severity of treatment-related adverse events (TRAEs). Secondary endpoints included radiological response and survival. Grade 3-4 TRAEs included arterial hypertension (n = 5) and proteinuria (n = 3), both related to bevacizumab, and diarrhea (n = 1), related to FMT. No serious TRAEs were observed. Objective response rate was 33% (n = 4/12) and median progression-free survival was 6.9 (95%CI, 3.0-10.8) months. Following FMT, recipient microbiome composition appeared more similar to that of the donor, and healthy donor FMT seemed to be associated with higher engraftment. FMT appeared to be associated with enrichment of response-associated and loss of deleterious gut bacteria. Circulating PD-1[+]CD8[+] T cells decreased and CD32b[+]CD14[high]CD16[low] monocytes increased following FMT plus immunotherapy. Phage-display immunoprecipitation sequencing revealed that antibody repertoire stability, rather than global diversity or composition, changed over time. Taken together, FMT combined with atezolizumab plus bevacizumab was safe and associated with a high response rate in patients with atezolizumab plus bevacizumab-refractory HCC. Given the limited sample size, these findings need cautious interpretation and confirmation in larger, adequately powered trials. ClinicalTrials.gov identifier: NCT05750030.},
}

Humans
*Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage/adverse effects
*Liver Neoplasms/therapy/immunology/mortality
Pilot Projects
*Bevacizumab/therapeutic use/administration & dosage/adverse effects
*Carcinoma, Hepatocellular/therapy/immunology/mortality
Female
Male
Middle Aged
*Fecal Microbiota Transplantation/methods/adverse effects
Aged
Immunotherapy/methods
Combined Modality Therapy
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Programmed Cell Death 1 Receptor/antagonists & inhibitors
Combined Antibody Therapeutics

@article {pmid42983789,
year = {2026},
author = {Chen, J and Guo, Z and Liu, M and Wei, Y and Wu, L and Li, J and Wang, W},
title = {Continuous fermentation-derived fecal microbiota transplantation improves intestinal barrier function and reshapes gut microbiota in weaned piglets.},
journal = {Animal microbiome},
volume = {8},
number = {1},
pages = {},
pmid = {42983789},
issn = {2524-4671},
abstract = {Weaning diarrhea in piglets poses a serious threat to the healthy development of the swine industry and is closely associated with gut microbiota dysbiosis. Fecal microbiota transplantation (FMT), as an effective strategy for modulating intestinal microecology, remains underexplored in swine production, particularly regarding the systematic evaluation of fecal microbiota suspension prepared via continuous fermentation on piglet health. In this study, fecal microbiota suspensions derived from adult pigs and piglets were prepared using a continuous fermentation system. A 28-day feeding trial was conducted with 18 piglets randomly assigned to three groups: control (CON), adult pig-derived FMT(FMT-A), and piglet-derived FMT(FMT-P). Growth performance, diarrhea incidence, gut microbiota, fecal short-chain fatty acids (SCFAs), and serum immune/inflammatory cytokines were measured. The results showed that compared with CON, both FMT treatments significantly increased average daily gain (ADG) and reduced diarrhea rate (P < 0.05), with FMT-A exhibiting superior effects to FMT-P. FMT improved intestinal barrier function, as evidenced by reduced serum levels of endotoxin (ET) and D-lactic acid (D-LA), raised immunoglobulin G (IgG) and anti-inflammatory cytokine interleukin-10 (IL-10), and lowered pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) (P < 0.05). FMT-A significantly reduced diamine oxidase (DAO) and increased immunoglobulin M (IgM) and immunoglobulin A (IgA) (P < 0.05). 16S rDNA sequencing revealed that FMT reshaped the intestinal microbiota: FMT-A enhanced microbial uniformity, FMT-P improved richness; both tended to increase beneficial Lactobacillus, with FMT-A significantly increasing Firmicutes(P < 0.05). Furthermore, FMT increased fecal propionic acid and decreased valeric acid (P < 0.05). This study demonstrates the efficacy of fecal microbiota suspension prepared via continuous fermentation technology in improving intestinal health and growth performance of piglets, providing a novel strategy for developing standardized, stable, and active microbe-based interventions, and laying a foundation for further mechanistic understanding of FMT in livestock production.},
}

@article {pmid42983933,
year = {2026},
author = {Patel, A and Jain, P},
title = {Why Gut-Brain Axis Therapies Fail in Clinical Translation: The Case for Endophenotyping and Longitudinal Trial Design.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X546118261028104240},
pmid = {42983933},
issn = {1875-6190},
abstract = {Although there is strong preclinical evidence for the involvement of the gut-brain axis in neuroimmune, metabolic and behavioural regulation, translation of gut-centric therapies to consistent clinical outcomes is challenging. Although probiotics, postbiotics, faecal microbiota transplants and mucosal anti-inflammatory treatments show therapeutic promise in animal studies, clinical trials often provide inconsistent or unclear results. One major reason for this translational gap is the biological heterogeneity hidden behind broad diagnostic categories. Individuals with the same clinical features can vary considerably in gut barrier function, mucosal immune responses, microbial community composition, microbial metabolite production, and systemic inflammatory pathways. Therapies targeting specific gut-brain pathways might, therefore, be tested in groups that include individuals without the relevant biological abnormality, potentially decreasing measurable therapeutic effects. There is a shift away from diagnosis-based recruitment toward mechanism-based endophenotyping. The integration of standardised composite inflammatory and metabolic endophenotypes with longitudinal host and microbial biomarkers could help to define physiologically meaningful therapeutic cohorts and differentiate between target engagement and clinical outcomes. Future studies should include initial stratification, ongoing biological sampling, and prospective validation of biomarkers that predict treatment response. Such an approach may turn seemingly ineffective therapies into mechanistic findings to identify patients most likely to benefit from changes in microbial, metabolic, or mucosal factors. Therefore, accurate endophenotyping may represent an important tool to bridge the translational gap from promising gut-brain studies to practical therapeutic interventions.},
}

@article {pmid42984552,
year = {2026},
author = {Rocchetti, A and Gotta, F and Bottino, P and Vay, D and Pizzo, V and Gugliotta, V and Grossi, AA and Besutti, V and Bianchetti, M and Bona, E and Castagliuolo, I and Corbella, M and Gasbarrini, A and Marangoni, A and Masucci, L and Mauro, MV and Putignani, L and Quaranta, G and Sanguinetti, M and Drago, L},
title = {Development and expert appraisal of a lifestyle questionnaire for microbiome host metadata.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1932122},
pmid = {42984552},
issn = {2235-2988},
mesh = {Humans ; Surveys and Questionnaires ; *Life Style ; *Metadata ; Italy ; *Gastrointestinal Microbiome ; *Microbiota ; Diet ; Sleep ; Exercise ; },
abstract = {INTRODUCTION: Lifestyle information can help contextualize variation in the human gut microbiome, but its collection and operational definitions differ across studies. We developed a candidate questionnaire combining diet, physical activity and sleep for microbiome host metadata and undertook an initial appraisal by Italian experts. Candidate content was informed by a focused narrative literature appraisal and established lifestyle-assessment frameworks.

METHODS: Seventeen experts were invited and nine responded (53%). In a single anonymous rating round, experts assessed the relevance of 37 candidate items on a five-point scale. The prespecified agreement criterion was at least 70% of respondents assigning a rating of 4 or 5, corresponding to at least seven of nine experts.

RESULTS: Twenty-five items (67.6%) met this criterion: 18 of 23 dietary items (78.3%), six of eight physicalactivity items (75.0%), and one of six sleep items (16.7%). Twelve items remained exploratory.

DISCUSSION: These findings provide an initial prioritization of candidate lifestyle metadata within an Italian specialist network. They do not establish a stable iterative Delphi consensus, instrument reliability, construct validity, or associations between questionnaire responses and microbiome outcomes. Participant testing, operational refinement and empirical evaluation are required before research deployment or potential use in fecal microbiota transplantation donor characterization.},
}

Humans
Surveys and Questionnaires
*Life Style
*Metadata
Italy
*Gastrointestinal Microbiome
*Microbiota
Diet
Sleep
Exercise

@article {pmid42984758,
year = {2026},
author = {Rawat, A and Prasad, N and Rawat, P and Ahmed, S and Kumar, B and Singh, A and Nayak, T and Kushwaha, RS},
title = {Beyond solute clearance: the kidney-gut-immune-nutrition axis in hemodialysis and peritoneal dialysis and a proposed framework for integrated risk stratification.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1931760},
pmid = {42984758},
issn = {2296-861X},
abstract = {Kidney disease affects approximately ~850 million people globally, with millions dependent on dialysis as life-sustaining renal replacement therapy. While dialysis corrects solute accumulation and fluid overload, it incompletely replicates normal renal physiology and introduces its own biological stressors, perpetuating a cycle of systemic dysfunction that extends well beyond the kidney. Central to this dysfunction is the kidney-gut-immune-nutrition (KGIN) axis: a bidirectional network linking renal clearance, intestinal microbial homeostasis, immune regulation, and nutritional metabolism. In end-stage renal disease, each component of this axis is simultaneously disrupted and becomes a driver of further deterioration. Uremic toxin accumulation remodels the gut microbiome toward a dysbiotic state, characterized by depletion of short-chain fatty acid-producing organisms and expansion of pathobionts. The resulting compromise of intestinal barrier integrity permits systemic translocation of lipopolysaccharide and other microbial products, sustaining chronic low-grade inflammation and a paradoxical state of immune dysfunction marked by heightened inflammatory signaling alongside impaired pathogen defense. These perturbations converge on nutritional status, driving protein-energy wasting through catabolic cytokine signaling, anorexia, and suppression of anabolic pathways, with sarcopenia reported in several dialysis cohorts to progress at two to three fold faster than age related muscle loss. Hemodialysis and peritoneal dialysis produce distinct patterns of axis disruption: hemodialysis is characterized by intermittent toxin peaks, bioincompatible membrane-driven complement activation, and more severe dysbiosis, whereas peritoneal dialysis introduces continuous peritoneal glucose exposure and a unique local immune microenvironment, with generally slower decline in residual kidney function. These modality-specific differences translate into divergent cardiovascular, infectious, and nutritional risk profiles that are incompletely explained by traditional clinical variables. Emerging multi-omics approaches, including metagenomics, metabolomics, and high-throughput immune profiling, are beginning to characterize axis disruption with unprecedented resolution, enabling in-depth characterization of host-microbiome-immune identification of patient subgroups with distinct mechanistic signatures that cannot be captured by single domain analysis alone. To bridge this analytical capability with clinical practice, we propose the Microbiome-Immune-Nutrition (MIN) Index, a conceptual, hypothesis generating composite biomarker framework designed to synthesize data across all three axis domains and stratify patients by the severity of disruption to guide targeted, personalized interventions, which remain to be demonstrated through prospective validation studies. Therapeutic strategies targeting the axis, including dietary fiber and plant-based approaches, synbiotics, fecal microbiota transplantation, advanced dialysis modalities, and omega-3 and polyphenol supplementation, show mechanistic promise but require larger, better-designed trials with hard clinical endpoints before routine clinical adoption. Standardization of microbiome research methodology, investment in longitudinal multi-omics cohorts, and development of international collaborative consortia are research priorities that will be essential to translate mechanistic insights into improvements in survival and quality of life for patients on maintenance dialysis.},
}

@article {pmid42984924,
year = {2026},
author = {Marano, G and Conci, L and Farsakh, L and Traversi, G and Mazza, O and Ricozzi, V and Rotondaro, S and Migliore, A and Capristo, E and Franceschini, G and Gaetani, E and Mazza, M},
title = {Microbiota Dysbiosis and the Gut-Brain Axis in Psychiatric Disorders: Molecular Mechanisms, Clinical Evidence, and Therapeutic Perspectives.},
journal = {Alpha psychiatry},
volume = {27},
number = {5},
pages = {54121},
pmid = {42984924},
issn = {2757-8038},
abstract = {The gut-brain axis provides a biologically plausible framework for understanding the bidirectional interactions among the intestinal microbiota, immune-inflammatory signaling, neuroendocrine regulation, neurotransmitter metabolism, and psychiatric symptoms. Although numerous recent reviews have examined individual psychiatric disorders, microbial composition, or microbiota-targeted therapies, the field still lacks a sufficiently integrated appraisal that clearly distinguishes associative findings from human studies, mechanistic evidence from preclinical research, and preliminary clinical interventions. This structured narrative review synthesizes clinical, translational, and preclinical studies across major depressive disorder, bipolar disorder, anxiety disorders, schizophrenia, and trauma-related conditions. The main literature search covered publications from January 2015 to January 2026; earlier foundational mechanistic studies of key relevance to gut-brain communication were also considered. Recurrent pathways include altered short-chain fatty acid production, tryptophan-kynurenine metabolism, immune-inflammatory activation, hypothalamic-pituitary-adrenal axis dysregulation, neurotransmitter-related signaling, impaired intestinal and blood-brain barrier integrity, and vagus nerve-mediated communication. Human studies predominantly demonstrate associations between microbial signatures and psychiatric phenotypes, symptom severity, inflammatory status, or treatment response, whereas preclinical models provide stronger mechanistic evidence that microbiota manipulation can influence behavioral, neurochemical, immune, and neuroendocrine outcomes. Probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation show therapeutic potential; however, the current evidence is limited by small sample sizes, methodological heterogeneity, insufficient standardization, and a lack of long-term validation. The distinctive contribution of this review is its structured comparison of three levels of evidence-human observational findings, experimental mechanistic studies, and emerging clinical interventions-thereby clarifying what has been consistently replicated, what remains mechanistically plausible, and what is not yet ready for routine application in psychiatric practice.},
}

@article {pmid42976978,
year = {2026},
author = {Ge, S and Li, L and Li, Y and Lv, S and Yang, Y and Liu, X and Wang, Y and Zhang, Y and Niu, L and Zhuang, P and Guo, H},
title = {Reversal of gut dysbiosis-related arachidonic acid deficiency alleviates Parkinsonian motor deficits and neuroinflammation.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {179501},
doi = {10.1016/j.ejphar.2026.179501},
pmid = {42976978},
issn = {1879-0712},
abstract = {Gut microbiota dysbiosis has been increasingly implicated in Parkinson's disease (PD), but the relationship of microbiota-associated metabolic alterations to PD remains poorly understood. This study investigated the association between gut microbiota dysbiosis and arachidonic acid (AA) dysregulation in PD and evaluated whether modulation of AA homeostasis could ameliorate Parkinsonian phenotypes. Gut microbial alterations were characterized by 16S rRNA gene sequencing, and serum metabolic changes were assessed using untargeted metabolomics combined with microbiota-metabolite correlation analysis. Marked gut microbiota dysbiosis was observed in PD mice and was accompanied by reduced serum AA levels. Fecal microbiota transplantation (FMT) increased serum AA levels and improved motor performance, providing functional support for a link between gut microbiota alterations and disrupted AA homeostasis. In addition, exogenous AA supplementation attenuated motor dysfunction and neuroinflammation. Collectively, these findings support a functional association among gut microbiota dysbiosis, altered AA homeostasis, and Parkinsonian phenotypes, suggesting that modulation of gut microbiota composition or AA availability may represent potential strategies for alleviating PD-associated motor dysfunction and neuroinflammation.},
}

@article {pmid42977101,
year = {2026},
author = {El-Sherbiny, GM},
title = {Reprogramming the tumor microbiome: Opportunities for cancer prevention, diagnosis, and precision therapy.},
journal = {Biochimica et biophysica acta. Reviews on cancer},
volume = {},
number = {},
pages = {189748},
doi = {10.1016/j.bbcan.2026.189748},
pmid = {42977101},
issn = {1879-2561},
abstract = {Microbiota-cancer interactions operate across distinct anatomical compartments, including the gut microbiota, the distal gut-tumor axis, and intratumoral microbiota residing within tumor tissues. These microbial communities and their metabolites can influence carcinogenesis, tumor progression, immune surveillance, and therapeutic responses through inflammation, genotoxicity, metabolic remodeling, epithelial and tumor-barrier dysfunction, and immune regulation. However, the magnitude and direction of these effects are highly context dependent, varying with cancer type, tumor site, microbial composition, host factors, treatment exposure, and methodological approaches. Importantly, associations between microbial signatures and clinical outcomes do not necessarily establish causality, and findings from gut microbiome studies should not be extrapolated directly to local intratumoral communities. This review critically synthesizes current evidence linking gut and intratumoral microbiota to tumor biology and treatment response, distinguishing compartment-specific mechanisms and evaluating the strength and limitations of available evidence. We examine how microbial metabolites, microbe-host interactions, and microbiota-driven immune and metabolic pathways shape the tumor microenvironment and may modify responses to immunotherapy, chemotherapy, radiotherapy, and targeted therapies. We further assess multi-omics and spatial approaches for resolving microbial heterogeneity and identifying clinically relevant biomarkers, alongside emerging microbiome-directed interventions, including probiotics, fecal microbiota transplantation, engineered microorganisms, and nanotechnology-based strategies. Particular emphasis is placed on discrepancies between preclinical and clinical findings, causal inference, reproducibility, interindividual variability, contamination and sampling challenges, and the barriers to clinical translation. Collectively, the evidence supports a context-specific role for microbiota in cancer biology while underscoring the need for standardized methodologies, longitudinal and mechanistic studies, and well-controlled clinical trials before microbiome-based strategies can be reliably incorporated into precision oncology.},
}

@article {pmid42979424,
year = {2026},
author = {Oulkadi, D and Van Oers, F and Vanden Driessche, L and Vandamme, S and Matheeussen, V and Mairesse, C and Martiny, D and Anguille, S and Demuyser, T},
title = {Persistent Campylobacter jejuni enterocolitis after CAR T-cell therapy in a patient with hypogammaglobulinemic follicular lymphoma.},
journal = {ASM case reports},
volume = {2},
number = {6},
pages = {},
pmid = {42979424},
issn = {2996-2684},
abstract = {BACKGROUND: Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide and typically results in self-limiting enterocolitis in immunocompetent individuals. In contrast, immunocompromised patients are at risk for severe, recurrent, or persistent infection. Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 induces prolonged B-cell aplasia and hypogammaglobulinemia, predisposing patients to atypical infections. We report the first case of persistent and disseminated C. jejuni infection following CD19-directed CAR T-cell therapy, confirmed by whole-genome sequencing.

CASE SUMMARY: A 68-year-old man with relapsed follicular lymphoma underwent autologous CD19-directed CAR T-cell therapy and achieved complete remission. Pre-existing hypogammaglobulinemia worsened after treatment. Eighteen months later, he developed recurrent bacteremia and chronic enterocolitis caused by C. jejuni. Over the following year, he experienced severe watery diarrhea, 20 kg weight loss, and disseminated infection with a prosthetic hip abscess. More than 10 stool cultures remained positive despite multiple antibiotic regimens and two fecal microbiota transplantations. Whole-genome sequencing demonstrated a single clonal strain with minimal variation, confirming persistent infection rather than reinfection. Microbiological clearance was achieved after 8 weeks of oral gentamicin, followed by 2 weeks of intravenous meropenem and azithromycin, with sustained negative cultures and PCR.

CONCLUSION: Persistent and disseminated C. jejuni infection can occur in patients with hypogammaglobulinemia after CD19-directed CAR T-cell therapy. Whole-genome sequencing may help distinguish persistence from reinfection. Standard immunoglobulin replacement may be insufficient due to limited IgA and IgM, and prolonged combination antimicrobial therapy may be required for durable remission.},
}

@article {pmid42979661,
year = {2026},
author = {Li, G and Dong, S and Liu, C and Yan, H and Yang, J and Rensen, PCN and Shi, B and Wang, Y},
title = {Dietary butyrate alleviates high-fat diet-induced colonic mucosal impairment accompanied by increased gut-derived indole-3-acetic acid and enhanced PPARγ signaling.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1971187},
pmid = {42979661},
issn = {1664-2392},
mesh = {Animals ; Male ; Mice ; *Diet, High-Fat/adverse effects ; *Intestinal Mucosa/metabolism/drug effects/pathology ; Humans ; *Colon/metabolism/drug effects/pathology ; *PPAR gamma/metabolism ; Gastrointestinal Microbiome/drug effects ; *Indoleacetic Acids/metabolism ; Signal Transduction/drug effects ; *Butyric Acid/pharmacology ; Caco-2 Cells ; Intestinal Barrier Function ; *Butyrates/pharmacology ; },
abstract = {INTRODUCTION: High-fat diet (HFD) induces intestinal barrier impairment, associated with gut microbiota dysbiosis, endotoxin translocation and metabolic dysfunction. Dietary butyrate has been reported to improve intestinal homeostasis, but the underlying mechanism remains incompletely understood. This study aimed to investigate the effects of dietary butyrate on HFD-induced colonic mucosal dysfunction and to explore underlying mechanisms with respect to the role of gut microbiota and its metabolites.

METHODS: Male APOE*3-Leiden.CETP mice, a well-established translational model for diet-induced metabolic dysfunction, were fed an HFD with or without 5% sodium butyrate. Metabolic phenotypes, plasma lipopolysaccharide (LPS), colonic histology, inflammatory responses, and tight junction-associated changes were assessed. Fecal microbiota transplantation (FMT) was performed in antibiotic-treated recipient mice to assess the contribution and transferability of butyrate-shaped gut microbiota. Cecal metagenomic sequencing and LC/MS-based colonic indole-3-acetic acid (IAA) measurement were performed. Caco-2 cells were used to assess the direct effects of sodium butyrate and IAA on enterocytes and to determine, through pioglitazone treatment and PPARγ knockdown, whether PPARγ mediates IAA-induced enterocyte responses.

RESULTS: Dietary butyrate induced favorable changes in multiple colonic barrier-associated parameters, including improved colonic architecture, lower circulating LPS levels, decreased Tnf-a and Il-1b expression, and increased CLDN2, Reg-family, and PPARγ expression in the colon. In addition, butyrate reduced body weight gain, fat mass accumulation and improved glucose metabolism. FMT from butyrate-treated donors partially reproduced these beneficial effects in HFD-fed recipients. Metagenomic analysis showed enrichment of Bacteroidota and Bacteroides, particularly B. uniformis and B. thetaiotaomicron, accompanied by increased colonic IAA levels. In Caco-2 cells, IAA increased the expression of PPARγ, Reg4, and CLDN2. While PPARγ agonist pioglitazone mimicked the upregulation of REG4 and CLDN2 expression by IAA, siRNA-induced PPARγ knockdown attenuated IAA-induced REG4 and CLDN2 upregulation.

CONCLUSION: Dietary butyrate improves colonic mucosal homeostasis under HFD feeding, accompanied by gut microbial remodeling and increased colonic IAA levels. Together with the PPARγ-dependent epithelial response to IAA observed in Caco-2 cells, these findings suggest a potential mechanistic framework linking butyrate-associated microbial changes, IAA metabolism, and epithelial PPARγ signaling.},
}

Animals
Male
Mice
*Diet, High-Fat/adverse effects
*Intestinal Mucosa/metabolism/drug effects/pathology
Humans
*Colon/metabolism/drug effects/pathology
*PPAR gamma/metabolism
Gastrointestinal Microbiome/drug effects
*Indoleacetic Acids/metabolism
Signal Transduction/drug effects
*Butyric Acid/pharmacology
Caco-2 Cells
Intestinal Barrier Function
*Butyrates/pharmacology

@article {pmid42979739,
year = {2026},
author = {Kumar, BK and Caputi, V and Gill, KK and Nanduri, B and Leroith, T and Fox, R and Rosa, F and Lyte, JM and Yeruva, L},
title = {Microbiota From Human Infants Consuming Secretors Mothers' Milk Affects Murine Intestinal Motility and Enteric Nervous System Development in a Sex-Dependent Manner.},
journal = {Neurogastroenterology and motility},
volume = {38},
number = {11},
pages = {},
pmid = {42979739},
issn = {1365-2982},
support = {6026-10700-001-000D//U.S. Department of Agriculture/ ; 6026-51000-012-000D//U.S. Department of Agriculture/ ; },
mesh = {Animals ; Female ; Male ; Humans ; *Enteric Nervous System/growth & development ; Mice ; *Milk, Human/microbiology ; Mice, Inbred C57BL ; *Gastrointestinal Motility/physiology ; Infant ; Sex Characteristics ; *Gastrointestinal Microbiome/physiology ; },
abstract = {BACKGROUND: Early life is a critical period in which the gut microbiome and the enteric nervous system (ENS) develop together, shaping long-term gastrointestinal (GI) function. Human milk feeding and particularly maternal secretor phenotype strongly influence early microbiome composition. However, how human milk promoted microbiomes impact ENS development is still largely unknown.

METHODS: Male and female juvenile (three weeks old) C57BL/6 germ-free mice were colonized with fecal microbiota from infants whose mothers were secretors (SMM, 2-fucosyl lactose in milk) or non-secretors (NSM) or from infants consuming cow's milk formula (MFM). Non-transplanted male and female germ-free mice served as controls. GI transit was assessed at post-natal day 35-37. ENS neuronal and glial organization was evaluated in full-thickness colon preparations using immunohistochemistry and confocal microscopy.

KEY RESULTS: Female germ-free mice receiving SMM exhibited higher distal GI transit efficiency and a higher proportion of nitrergic neurons in the myenteric plexus compared to sex-matched controls and to males. Choline acetyltransferase (ChAT; marker for excitatory cholinergic neurons) immunoreactivity was higher in the myenteric ganglia of germ-free female compared to male mice. ChAT immunoreactivity increased in SMM and MFM males, while it was significantly reduced in NSM and MFM females compared to controls. Infant microbiomes did not affect myenteric glial cells, which were more abundant in males than females across all groups.

CONCLUSIONS AND INFERENCES: Our findings demonstrate that early-life maternal secretor-associated infant microbiomes exert sex-specific effects on ENS neuronal phenotypes and GI motility, underlying a previously unrecognized link between infant-derived microbiomes and ENS development that warrants investigation in larger cohorts.},
}

Animals
Female
Male
Humans
*Enteric Nervous System/growth & development
Mice
*Milk, Human/microbiology
Mice, Inbred C57BL
*Gastrointestinal Motility/physiology
Infant
Sex Characteristics
*Gastrointestinal Microbiome/physiology

@article {pmid42980207,
year = {2026},
author = {Mutanen, A and Pini Prato, A and Erculiani, M and Lambe, C and Lindert, J and Märzheuser, S and Fusaro, F and Stensrud, KJ and Bjornland, K and Qvist, N and Ellebæk, MB and Tabbers, MM and Derikx, JPM and Sfeir, R and Reinshagen, K and Ludwiczek, J and Poš, L and Bartošová, T and Miserez, M and Granström, AL and Wester, T and Hilberath, J and Bonnard, A and Di Fabrizio, D and Guz-Mark, A and Poinsot, P and Van Renterghem, K and Destro, F and Stenström, P and Friedmacher, F and Rolle, U and Coletta, R and Morabito, A and Fascetti Leon, F and Duci, M and Sloots, CEJ and Versteegh, H and Atouguia, D and Campos, M and Spector Cohen, I and Cavar, S and Sabolic, I and Tarrado, X and Langer, S and Norsa, L and Pakarinen, MP},
title = {Long-term outcomes after total colonic aganglionosis: retrospective European multicentre cohort study.},
journal = {BJS open},
volume = {10},
number = {6},
pages = {},
pmid = {42980207},
issn = {2474-9842},
support = {//The Foundation for Pediatric Research, Finland/ ; },
mesh = {Humans ; *Hirschsprung Disease/surgery/genetics/mortality ; Retrospective Studies ; Europe/epidemiology ; Female ; Male ; Cross-Sectional Studies ; Child, Preschool ; Child ; Adolescent ; Treatment Outcome ; Postoperative Complications/epidemiology ; Colorectal Surgical Procedures ; },
abstract = {BACKGROUND: Total colon aganglionosis (TCA), a severe form of Hirschsprung disease, is a rare and complex condition with variable management and limited outcome data. This retrospective cross-sectional multicentre study assessed current long-term outcomes of TCA in Europe.

METHODS: Patients with TCA under follow up at participating ERNICA and ESPGHAN centres were included. Data were collected on genetics, nutritional, functional, and surgical outcomes, intestinal inflammatory lesions, and mortality during the preceding 10 years.

RESULTS: Thirty-one centres from 15 countries contributed 401 patients (median age 7.9 years; interquartile range 4.0-13.6 years). Genetic testing was performed in 52% of patients, with pathogenic variants identified in 62%, mainly RET. Aganglionosis was limited to the colon in 26%, extended to the small bowel in 71%, and was total intestinal in 3%, without association with genetic status. At the latest follow-up, 25% of patients were receiving parenteral nutrition (PN); PN dependency was associated with small intestine extension of aganglionosis > 50 cm (72% of patients with >50 cm small bowel aganglionosis versus 15% of patients aganglionosis <50 cm small bowel or limited to the colon; P < 0.001). Overall, 77% of patients underwent pull-through, most commonly ileoanal anastomosis (62%) or Duhamel (31%). Complications included anastomotic leak (4%), strictures (12%), redo surgery (24%), recurrent enterocolitis (36%), obstructive symptoms (24%), and faecal incontinence (25%). Recurrent enterocolitis was associated with obstructive symptoms (P = 0.007). Endoscopy showed intestinal inflammatory lesions in 22% of patients, particularly those with recurrent enterocolitis (odds ratio (OR) 6.43; 95% confidence interval (c.i.) 3.27 to 12.63) and obstructive symptoms (OR 2.64; 95% c.i. 1.26 to 5.53). The 10-year mortality rate was 3.4%.

CONCLUSION: TCA shows a high prevalence of genetic abnormalities and substantial postoperative and long-term morbidity, independent of surgical technique.},
}

Humans
*Hirschsprung Disease/surgery/genetics/mortality
Retrospective Studies
Europe/epidemiology
Female
Male
Cross-Sectional Studies
Child, Preschool
Child
Adolescent
Treatment Outcome
Postoperative Complications/epidemiology
Colorectal Surgical Procedures

@article {pmid42971666,
year = {2026},
author = {Frandsen, EV and Hvas, CL and Baunwall, SMD and Friis, RB and Guldbrandt, LM and Schmidt, H},
title = {Faecal microbiota transplantation to enhance immune checkpoint inhibitor response in solid cancers: a systematic review.},
journal = {Best practice & research. Clinical gastroenterology},
volume = {83},
number = {},
pages = {102152},
doi = {10.1016/j.bpg.2026.102152},
pmid = {42971666},
issn = {1532-1916},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Immune Checkpoint Inhibitors/therapeutic use ; *Neoplasms/therapy/drug therapy/immunology ; Treatment Outcome ; Combined Modality Therapy ; },
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) are pivotal in cancer treatment, but some patients develop resistance. In this systematic review, we aimed to summarise efficacy and safety of faecal microbiota transplantation (FMT) to enhance ICI therapy responses in patients with solid cancers.

METHODS: We systematically searched PubMed, Embase and Web of Science on May 12, 2025 for studies evaluating FMT in combination with ICI for solid cancers.

RESULTS: We included five clinical trials, of which none included comparator therapy, describing 78 patients. Notably, some patients previously refractory to anti-PD-1 therapy achieved partial or complete responses following FMT combined with ICIs. Assessing safety, 76% had grade 1-2 adverse events, and grade ≥3 events were only observed after ICI initiation.

CONCLUSION: Small uncontrolled studies indicate a potential effect for FMT to enhance efficacy of ICI therapy without increasing toxicity.},
}

Humans
*Fecal Microbiota Transplantation/methods/adverse effects
*Immune Checkpoint Inhibitors/therapeutic use
*Neoplasms/therapy/drug therapy/immunology
Treatment Outcome
Combined Modality Therapy

@article {pmid42971669,
year = {2026},
author = {Margarita, E and Saito, K and Bisegna, P and Ferrari, M and Valeriani, E and Guerrieri, M and Funaro, B and Feliciani, D and Gasbarrini, A and Porcari, S and Ianiro, G},
title = {Gut microbiome in immuno-oncology: potential for clinical exploitation.},
journal = {Best practice & research. Clinical gastroenterology},
volume = {83},
number = {},
pages = {102143},
doi = {10.1016/j.bpg.2026.102143},
pmid = {42971669},
issn = {1532-1916},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Neoplasms/immunology/therapy/microbiology/drug therapy ; Probiotics/therapeutic use ; *Immune Checkpoint Inhibitors/therapeutic use/adverse effects ; *Immunotherapy/methods/adverse effects ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; },
abstract = {Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of multiple malignancies, yet durable clinical benefit remains limited to a subset of patients, while immune-related adverse events still represent a major therapeutic challenge. Over the past decade, compelling evidence has established the gut microbiota as a key host determinant of both the efficacy and toxicity of cancer immunotherapy. Given its profound diversity and plasticity, as well as its impact on systemic immunity, gut commensals are now considered as both a promising predictive biomarker of response and a potentially actionable therapeutic target. As a result, different microbiota-informed approaches are being explored for precision immune-oncology. Specifically, emerging biomarker strategies are moving beyond single bacterial taxa toward ecological and functional microbial signatures with improved reproducibility across patient cohorts. At the same time, therapeutic modulation of the gut microbiome, through dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation, is being actively investigated to enhance responsiveness to ICIs and mitigate immune-related adverse events. In this review, we discuss the biological mechanisms linking gut microbiota and immunotherapy, evaluate its role as biomarker and therapeutic target, and address the current challenges that need to be overcome to integrate microbiota into precision immune-oncology.},
}

Humans
*Gastrointestinal Microbiome/immunology/drug effects
*Neoplasms/immunology/therapy/microbiology/drug therapy
Probiotics/therapeutic use
*Immune Checkpoint Inhibitors/therapeutic use/adverse effects
*Immunotherapy/methods/adverse effects
Fecal Microbiota Transplantation
Prebiotics/administration & dosage

@article {pmid42973594,
year = {2026},
author = {Wang, L and Xie, J and Sun, Y and Zhang, Y and Gao, X and Li, Y and Liu, L},
title = {Akkermansia muciniphila improves synaptic remodeling and alleviates sepsis-associated cognitive dysfunction via regulating the gut-brain axis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1925161},
pmid = {42973594},
issn = {1664-3224},
mesh = {Animals ; Mice ; *Sepsis/complications/microbiology ; *Neuronal Plasticity ; Male ; *Cognitive Dysfunction/etiology ; Disease Models, Animal ; Gastrointestinal Microbiome ; *Brain-Gut Axis ; Mice, Inbred C57BL ; Hippocampus/metabolism ; Intestinal Barrier Function ; Akkermansia ; Fecal Microbiota Transplantation ; Synapses ; },
abstract = {BACKGROUND: Sepsis-associated cognitive impairment (SACI) is a frequent long-term complication of sepsis characterized by hippocampal neuroinflammation, synaptic loss and gut microbial dysbiosis. Akkermansia muciniphila (AKK) possesses anti-inflammatory and intestinal barrier-protective functions, yet its role and mechanism in SACI remain poorly understood.

METHODS: In this study, a CLP-induced septic mouse model was used to explore the protective effect of AKK. Behavioral tests were performed to evaluate anxiety and cognitive function. Hippocampal neuronal injury, microglial activation and synaptic plasticity were assessed by HE staining, immunofluorescence, Western blotting and TEM. Intestinal barrier function, gut microbiota composition and metabolic profiles were analyzed via 16S rRNA sequencing and untargeted metabolomics, with FMT applied for mechanistic verification.

RESULTS: AKK intervention remarkably alleviated anxiety-like behaviors and rescued cognitive deficits in septic mice. AKK inhibited microglial overactivation, activated the BDNF/P-TrkB pathway, and restored the expression of synaptic SYP and PSD95. Meanwhile, AKK preserved intestinal tight junction integrity, reshaped gut microbiota structure, and reversed sepsis-related metabolic disturbances. FMT further provided evidence that AKK-modulated gut microbiota improved survival and cognitive performance.

CONCLUSION: In conclusion, AKK ameliorates SACI by suppressing hippocampal neuroinflammation, restoring synaptic plasticity and remodeling the microbiota-gut-brain axis, indicating its potential as a promising candidate for SACI intervention.},
}

Animals
Mice
*Sepsis/complications/microbiology
*Neuronal Plasticity
Male
*Cognitive Dysfunction/etiology
Disease Models, Animal
Gastrointestinal Microbiome
*Brain-Gut Axis
Mice, Inbred C57BL
Hippocampus/metabolism
Intestinal Barrier Function
Akkermansia
Fecal Microbiota Transplantation
Synapses

@article {pmid42974254,
year = {2026},
author = {El-Sayed Ahmed, MAE and El-Lakany, RR and Ramadan, M and Goda, RM},
title = {Clostridioides difficile infections and beyond: molecular epidemiology, One Health transmission chains, under-surveilled regions, and the next generation of diagnostics, therapeutics, and vaccines.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1992944},
pmid = {42974254},
issn = {2235-2988},
mesh = {Humans ; *Clostridioides difficile/genetics/classification/isolation & purification ; Molecular Epidemiology ; *Clostridium Infections/epidemiology/diagnosis/transmission/prevention & control/drug therapy/therapy/microbiology ; *One Health ; Animals ; Whole Genome Sequencing ; Bacterial Vaccines/immunology ; Cross Infection/epidemiology/transmission/microbiology ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Ribotyping ; },
abstract = {Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhea and an urgent antimicrobial resistance threat, but the organism clinicians now face differs from the one that drove the ribotype 027 epidemics. This review is organized around a single question: which parts of the C. difficile transmission and treatment cycle are invisible to the methods used to observe them? Four developments define the answer. First, whole-genome sequencing consistently identifies genomic links between hospital cases that ward-based contact tracing cannot reconcile, and isolates from asymptomatically colonized patients are linked to subsequent cases as often as those from symptomatic patients, in some instances many months after an index encounter; we read a four-year single-center study from Guangzhou, China, in which one author participated, alongside comparable cohorts from England, Denmark and Canada. Second, One Health genomics places human and non-human compartments within a single transmission network, though the direction of transfer and the attributable fraction of human disease remain unquantified. Sequence type 11 and its ribotype 078 sublineage circulate between livestock and humans at clonal resolution, cryptic clades meet species-level divergence thresholds, and community-associated disease accounts for roughly a third of cases. Third, resistance to first-line therapy now has defined molecular mechanisms, including plasmid-borne and heme-dependent metronidazole resistance, constitutive vanG expression underlying reduced vancomycin susceptibility, and RNA polymerase substitutions conferring reduced fidaxomicin susceptibility that emerge during treatment; several of these are undetectable under standard laboratory conditions. Fourth, pathogenesis is being reframed as polymicrobial, with enterococci cross-feeding leucine and ornithine while depleting arginine as a virulence cue. We integrate these strands with age-stratified vulnerability in older and pediatric patients, with the diagnostic problem of separating infection from colonization, and with the diverging regulatory frameworks that now separate donor-derived fecal microbiota transplantation from licensed live biotherapeutic products.},
}

Humans
*Clostridioides difficile/genetics/classification/isolation & purification
Molecular Epidemiology
*Clostridium Infections/epidemiology/diagnosis/transmission/prevention & control/drug therapy/therapy/microbiology
*One Health
Animals
Whole Genome Sequencing
Bacterial Vaccines/immunology
Cross Infection/epidemiology/transmission/microbiology
Anti-Bacterial Agents/therapeutic use/pharmacology
Ribotyping

@article {pmid42976410,
year = {2026},
author = {Shimoyama-Ibuki, S and Iyama, S and Shirato, S and Sato, K and Yoshida, M and Goto, A and Horiguchi, H and Kobune, M},
title = {Longitudinal changes in diamine oxidase activity and gut microbiota in hematopoietic stem cell transplantation recipients.},
journal = {Leukemia research},
volume = {171},
number = {},
pages = {108358},
doi = {10.1016/j.leukres.2026.108358},
pmid = {42976410},
issn = {1873-5835},
abstract = {BACKGROUND: Gut microbiota disruption and intestinal epithelial injury are associated with acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated longitudinal changes in the gut microbiota, circulating diamine oxidase (DAO), and short-chain fatty acids (SCFAs) in relation to GVHD.

METHODS: Eighteen allo-HSCT recipients were retrospectively analyzed. Plasma DAO activity and serum DAO concentration were measured before conditioning and on days 14, 28, and 60 after HSCT, and plasma SCFAs before and after HSCT. Pre- and post-HSCT fecal samples underwent 16S rRNA gene sequencing.

RESULTS: Nine patients developed grade 2-4 acute GVHD. DAO activity decreased significantly after HSCT, particularly in patients who developed GVHD. Changes in DAO activity showed a moderate, nonsignificant positive correlation with changes in the relative abundance of the [Eubacterium] hallii group. Before HSCT, Eubacterium was significantly more abundant in patients who did not subsequently develop GVHD. Pre- to post-HSCT Bray-Curtis dissimilarity was greater in the GVHD group than in the non-GVHD group, although not significantly. In the GVHD group, several butyrate-associated taxa, including Ruminococcaceae, the Clostridium methylpentosum group, and Oscillospirales, were depleted after HSCT. SCFA concentrations did not differ significantly by GVHD status and were not significantly associated with the relative abundance of the [Eubacterium] hallii group after correction for multiple testing.

CONCLUSIONS: Patients who developed acute GVHD showed altered gut microbial composition, including depletion of butyrate-associated taxa, together with decreased DAO activity. These exploratory findings suggest a potential relationship between gut microbial alterations and intestinal epithelial integrity after allo-HSCT.},
}

@article {pmid42976420,
year = {2026},
author = {Rendeiro, J and Santos, VH and Silva-Vaz, P},
title = {Psychobiotic modulation of the microbiome-gut-brain axis: A systematic review of the literature.},
journal = {Psychoneuroendocrinology},
volume = {195},
number = {},
pages = {108064},
doi = {10.1016/j.psyneuen.2026.108064},
pmid = {42976420},
issn = {1873-3360},
abstract = {BACKGROUND: Major depressive disorder (MDD) is incompletely explained by the monoaminergic model. The microbiome-gut-brain (MGB) axis may link gut microbial ecology to immune, metabolic, neuroendocrine and neural signalling relevant to mood and antidepressant response.

OBJECTIVES: To synthesise recent evidence on (I) microbiota-targeted (psychobiotic) interventions; (II) the gut microbiome as a diagnostic and treatment-response biomarker; and (III) biopsychosocial and immunometabolic correlates of depression.

METHODS: PubMed, Scopus and PubPsych were searched (January 2022 to February 2025) following PRISMA 2020. Risk of bias was assessed with RoB 2, ROBINS-I and the Newcastle-Ottawa Scale. Findings were synthesised narratively, stratified by population, intervention type and study design.

RESULTS: Sixty-six studies were included: 36 in diagnosed depressive disorders, 10 in non-clinical samples, 15 in other medical conditions and 5 genetic or biobank analyses; most were of low or very low methodological quality. Depression was associated with lower abundance of short-chain fatty acid-producing taxa and with altered tryptophan, bile acid, inflammatory and barrier-related markers, largely in cross-sectional designs. In MDD, some strain-specific add-on probiotics were associated with greater symptom reduction than placebo, whereas others showed no benefit; prebiotic, dietary and faecal microbiota transplantation data were sparse or derived from non-MDD populations. Diagnostic and treatment-response models came from small samples and were rarely externally validated.

CONCLUSIONS: The gut microbiome is a plausible contributor to depressive pathophysiology and treatment variability, but current evidence is heterogeneous, predominantly associative and of low certainty. Psychobiotic interventions and microbiome-based biomarkers remain investigational; adequately powered, strain- and dose-specific trials and independently validated models are required before clinical application.},
}

@article {pmid42967431,
year = {2026},
author = {Zhang, Q and Xu, J and Jiang, W and Jia, Q and Jiang, X and Zhang, L and Alhaskawi, A and Sun, R and Sun, Y and Wang, X and Zhao, F},
title = {Multi-omics reveals that polystyrene microplastic exposure induces bone loss in mice by disrupting intestinal glycine metabolism.},
journal = {Ecotoxicology and environmental safety},
volume = {326},
number = {},
pages = {121005},
doi = {10.1016/j.ecoenv.2026.121005},
pmid = {42967431},
issn = {1090-2414},
abstract = {Polystyrene microplastic exposure induced a pronounced bone-loss phenotype in C57BL/6 mice, characterized by reduced bone density and trabecular bone volume together with impaired osteogenic differentiation. To determine whether this skeletal toxicity was mediated by the gut microenvironment, we performed fecal microbiota transplantation and found that microbiota from microplastic-exposed donors was sufficient to recapitulate bone loss in recipient mice, supporting a causal role for microbiota alterations. Consistent with this mechanism, recipients exhibited compromised intestinal barrier integrity and heightened intestinal inflammation, alongside a dysbiotic microbial profile marked by depletion of beneficial taxa and enrichment of pro-inflammatory bacteria. Integrative multi-omics analyses further connected these gut changes to osteogenic dysfunction, revealing suppression of osteogenesis-related programs and inhibition of key signaling pathways, including PI3K-AKT and WNT/β-catenin signaling. Finally, metabolomic findings guided the selection of glycine for supplementation, which, when initiated concurrently with FMT, attenuated the development of bone loss in recipients receiving fecal microbiota from PS-MP-exposed donors.},
}

@article {pmid42967725,
year = {2026},
author = {Bai, L and Liu, L and Song, C and Zhao, Z and Chu, G and Ren, X and Ai, C and Song, S},
title = {Gut microbiota-dependent immunomodulatory effects of galactofucan: Evidence from fecal microbiota transplantation and pseudo-germ-free mice.},
journal = {Food research international (Ottawa, Ont.)},
volume = {245},
number = {Pt 4},
pages = {120909},
doi = {10.1016/j.foodres.2026.120909},
pmid = {42967725},
issn = {1873-7145},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation ; Mice ; Intestinal Barrier Function ; *Polysaccharides/pharmacology ; Mice, Inbred C57BL ; Male ; Dysbiosis ; Germ-Free Life ; *Immunologic Factors/pharmacology ; CD4-Positive T-Lymphocytes ; },
abstract = {In recent years, the relationship between the immunomodulatory mechanisms of fucoidans and the gut microbiota has attracted widespread attention. However, there is currently a lack of direct evidence confirming that gut microbiota is essential for fucoidan to exert its immunomodulatory functions. Therefore, the present study employed fecal microbiota transplantation (FMT) and pseudo-germ-free (PGF) mouse models to investigate the mechanism underlying the immunomodulatory activity of Undaria pinnatifida sporophyll galactofucan (UPSG). The results showed that recipients transplanted with UPSG-derived microbiota increased the proportions of CD4[+] and CD8[+] T lymphocytes to 1.8-fold of those in the CTX-FMT group, respectively, and alleviated intestinal barrier damage. In addition, UPSG-derived microbiota transplantation restored gut microbial dysbiosis, markedly enriched Muribaculaceae, and ameliorated metabolic disturbances accompanied by elevated guanidoacetic acid level. In contrast, depletion of the gut microbiota abolished the protective effects of UPSG on systemic immune function and intestinal barrier integrity. Collectively, these results demonstrated the immunomodulatory effects of UPSG depend on the presence of the gut microbiota and provides experimental evidence supporting the involvement of the gut microbiota in the immunomodulatory mechanism of UPSG.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Fecal Microbiota Transplantation
Mice
Intestinal Barrier Function
*Polysaccharides/pharmacology
Mice, Inbred C57BL
Male
Dysbiosis
Germ-Free Life
*Immunologic Factors/pharmacology
CD4-Positive T-Lymphocytes

@article {pmid42969769,
year = {2026},
author = {Huang, X and Wang, Y and Meng, Z and Zheng, P},
title = {The three-layer defense system of gut microbiota in regulating bone development and homeostasis: homeostatic maintenance, stress sensing, and programmed repair.},
journal = {EFORT open reviews},
volume = {11},
number = {11},
pages = {1211-1227},
doi = {10.1530/EOR-2026-0067},
pmid = {42969769},
issn = {2058-5241},
abstract = {The gut microbiota functions as a critical regulator of bone development and homeostasis through a proposed 'three-layer defense system': basal homeostatic maintenance, danger sensing, and active repair. Microbial metabolites such as short-chain fatty acids, tryptophan derivatives, and vitamin K modulate bone metabolism via GPCR signaling, epigenetic regulation, and immune modulation, establishing a foundation for skeletal health. Endocrine axes - including estrogen, GH/IGF-1, and PTH - interact with the gut microbiota to influence bone remodeling, with dysbiosis contributing to inflammatory amplification and osteoclast activation via RANKL/NF-κB pathways. The third-layer defense involves targeted repair through probiotics and bacterial extracellular vesicles, which restore immune homeostasis, enhance osteogenesis, and suppress bone resorption. Therapeutic strategies targeting this multi-layer system - including probiotic interventions, fecal microbiota transplantation, and bioactive compound supplementation - offer promising avenues for personalized prevention and treatment of metabolic bone diseases.},
}

@article {pmid42970314,
year = {2026},
author = {Xu, J and Cao, Z and Liu, Y and Gao, A and Kong, Y},
title = {Fecal Microbiota Transplantation in Alzheimer's Disease: A Scoping Review of Human, Registry, and Preclinical Evidence.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2026.0883},
pmid = {42970314},
issn = {2152-5250},
abstract = {Fecal microbiota transplantation (FMT) is being explored as a microbiota-directed intervention for Alzheimer's disease (AD), with evidence drawn mainly from preclinical studies. This scoping review mapped published human reports, registered trials and animal microbiota-transfer studies to inform FMT research in AD. Five human reports, eight unique registered trials and 34 animal studies were included. Four human reports concerned FMT administered for Clostridioides difficile infection (CDI). The remaining report was an uncontrolled five-patient pilot comprising two patients with AD, two with mild cognitive impairment (MCI) and one with frontotemporal dementia (FTD). It described maintained cognition in AD and FTD and improvement or maintenance in MCI. The published human studies were nonrandomized. Among the eight registered trials, two required AD biomarker confirmation and two specified donor-referenced engraftment outcomes. Among 30 animal studies assessing cognition, 24 reported positive findings and six mixed findings. Restriction to genetic/transgenic AD models reduced the positive proportion from 24/30 (80.0%) to 17/23 (73.9%). Cognition-specific randomization and blinding were reported in 16/30 (53.3%) and 4/30 (13.3%) studies, respectively. The evidence supports early-phase investigation, with attention to donor and product characterization, appropriate comparators, and separate measurement of engraftment, microbial function, systemic responses and AD outcomes. Safety data remain insufficient for patients with AD, particularly outside the CDI setting. FMT should remain investigational for AD.},
}

@article {pmid42971661,
year = {2026},
author = {Nikitina, D and Morkunas, E and Sabanas, P and Jonaitis, P and Urbonas, T and Gedgaudiene, G and Gedgaudas, R and Kupcinskiene, K and Macas, A and Simenas, S and Kiudelyte, D and Buginyte, R and Vitkauskiene, A and Poskiene, L and Strati, F and Skieceviciene, J and Kupcinskas, J},
title = {Microbiome testing in gastrointestinal cancers: From microbial signatures to clinical translation.},
journal = {Best practice & research. Clinical gastroenterology},
volume = {83},
number = {},
pages = {102127},
doi = {10.1016/j.bpg.2026.102127},
pmid = {42971661},
issn = {1532-1916},
mesh = {Humans ; *Gastrointestinal Neoplasms/microbiology/therapy/immunology ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/microbiology/therapy/immunology ; Fecal Microbiota Transplantation ; Translational Research, Biomedical ; Precision Medicine ; Immune Checkpoint Inhibitors/therapeutic use ; },
abstract = {The gastrointestinal microbiome has emerged as a critical interface between environmental exposures and host biology, shaping carcinogenesis, tumor behavior, and therapeutic responsiveness across digestive tract malignancies. This narrative review synthesizes current evidence on microbiome testing in esophageal, gastric, colorectal, hepatobiliary, pancreatic, and gastrointestinal stromal cancers, highlighting microbial signatures, emerging translational applications, and the methodological challenges that currently limit clinical implementation. Tumor-specific microbial alterations are considered alongside the broader functional consequences of dysbiosis, including its roles in genotoxicity, immune modulation, and metabolic reprogramming. Particular attention is given to the influence of the microbiome on systemic therapies, especially immune checkpoint inhibition, where microbial diversity, compositional signatures, and antibiotic exposure have been associated with differences in treatment efficacy. Emerging mechanistic insights are highlighted, including the role of microbiota-derived metabolites as key mediators of host-tumor immune interactions. The review further discusses microbiome-directed interventions, including fecal microbiota transplantation and dietary modulation, while critically evaluating the barriers to their clinical translation. Although microbiome profiling has considerable potential to improve risk stratification and therapeutic personalization, current evidence remains largely associative or based on early-phase clinical studies, and no microbiome-based testing strategy has yet been validated for routine clinical use beyond Helicobacter pylori eradication for gastric cancer prevention. Large prospective studies, standardized methodologies, and interventional clinical trials are required before microbiome testing can be integrated into routine precision oncology.},
}

Humans
*Gastrointestinal Neoplasms/microbiology/therapy/immunology
*Gastrointestinal Microbiome/immunology
*Dysbiosis/microbiology/therapy/immunology
Fecal Microbiota Transplantation
Translational Research, Biomedical
Precision Medicine
Immune Checkpoint Inhibitors/therapeutic use

@article {pmid42964097,
year = {2026},
author = {Savytska, M and Halich, VS and Kuzmenko, L and Halabitska, I and Kamyshna, I and Petakh, P and Kamyshnyi, O and Kobyliak, N},
title = {Effects of faecal microbiota transplantation on glycaemic outcomes in adults with metabolic disorders: a systematic review and meta-analysis of randomised controlled trials.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1983162},
pmid = {42964097},
issn = {2296-858X},
abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) may improve glucose metabolism, but findings from randomised trials and previous meta-analyses are inconsistent. We evaluated the effects of FMT on glycaemic outcomes in adults with type 2 diabetes, prediabetes, insulin resistance or related metabolic disorders.

METHODS: We searched PubMed and Scopus for English-language randomised controlled trials published from January 2000 to May 2026. The primary outcome was change from baseline in HOMA-IR. Secondary outcomes included HbA1c, fasting glucose and clamp-derived peripheral insulin sensitivity. Random-effects meta-analyses used Paule-Mandel estimation with Hartung-Knapp-Sidik-Jonkman confidence intervals. Sensitivity analyses evaluated comparator type, data reconstruction, the assumed baseline-follow-up correlation and individual-study influence. Risk of bias was assessed using RoB 2.

RESULTS: The searches identified 887 records, and 18 studies met the eligibility criteria. Six trials involving 120 participants included to the primary analysis. FMT did not significantly reduce HOMA-IR compared with control (MD, -1.29; 95% CI [-3.04, 0.47]; I[2] = 72%). The sensitivity analysis combining HOMA-IR and HOMA2-IR also produced a non-significant result (MD, -1.11; 95% CI [-2.50, 0.29]). HbA1c data were sparse and were not pooled across comparator types. Clamp-derived findings suggested a possible donor-phenotype effect but remained inconclusive. The certainty of evidence was very low for HOMA-IR and HbA1c and low for peripheral insulin sensitivity.

CONCLUSIONS: FMT did not demonstrate a clear benefit for glycaemic outcomes. The estimates were imprecise, heterogeneous and influenced by comparator design. Larger trials with standardised outcomes and predefined donor phenotypes are required.},
}

@article {pmid42964834,
year = {2026},
author = {Al-Beltagi, M and Saeed, NK and Elbeltagi, YM},
title = {Psychobiotics in pediatric autism spectrum disorder: A systematic review of efficacy, mechanisms, and clinical translation.},
journal = {World journal of clinical pediatrics},
volume = {15},
number = {4},
pages = {121115},
pmid = {42964834},
issn = {2219-2808},
abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition frequently associated with gastrointestinal (GI) disturbances and alterations in gut microbiota composition. Increasing evidence suggests that the microbiota-gut-brain axis may play a role in the pathophysiology of ASD, raising interest in microbiome-targeted therapies, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT). However, the clinical effectiveness and mechanisms of these interventions remain incompletely understood due to heterogeneous study designs and variable outcomes across trials.

AIM: To systematically evaluate the clinical efficacy and mechanistic implications of psychobiotic interventions, including probiotics, prebiotics, synbiotics, and FMT, in children with ASD.

METHODS: We conducted this systematic review in accordance with PRISMA 2020 guidelines. We also followed the methodological recommendations of the Cochrane Handbook. We searched different electronic databases, including PubMed/MEDLINE, EMBASE, Web of Science, PsycINFO, CENTRAL, and CINAHL, from inception till February 2026. We included eligible randomized controlled trials, controlled clinical trials, cohort studies, and pre-post intervention studies evaluating psychobiotic therapies in children and adolescents (≤ 18 years) with ASD. The main outcomes were: (1) Changes in severity as assessed by a broad-spectrum measure of ASD symptomatology at the 3-month follow-up; and (2) Variation of core symptoms, based on validated behavioral scales, including the Autism Diagnostic Observation Schedule, the Childhood Autism Rating Scale (CARS), and the Social Responsiveness Scale (SRS). We measured the severity of GI symptoms, microbiome composition, biologicals, and safety as secondary outcomes. Risk of bias was determined with Risk of Bias tool version 2 and Risk of Bias in Non-randomized Studies of Interventions tools. Meta-analysis using random-effects models was conducted where appropriate.

RESULTS: We reviewed 35 clinical studies that examined microbiome-targeted therapies in children with ASD. Overall, probiotics were associated with obvious improvements in GI symptoms and smaller, but noticeable, improvements in behavioral outcomes, although the benefits varied depending on the probiotic strains used, treatment duration, and whether children had GI problems at baseline. When data from selected probiotic studies were pooled, a moderate-to-large overall benefit was observed for GI symptom severity. Prebiotic supplementation mainly benefited gut function and microbial metabolic activity, with little and inconsistent impact on core autism symptoms. Synbiotic approaches-which combine probiotics with fermentable substrates-produced broader effects on the gut microbiome and were linked to modest improvements in both GI and behavioral symptoms. We observed that FMT showed the strongest overall effects among all microbiome-based interventions. Using quantitative analyses, we observed marked improvements in GI symptoms (GI SRS pooled SMD -2.71), along with a significant decrease in key behavioral measures, including social responsiveness (SRS pooled SMD -4.06), aberrant behavior (Aberrant Behavior Checklist -3.00), and overall autism severity (CARS -1.60). However, the strength of this evidence is tempered by the fact that many FMT studies were open-label or non-randomized, which limits confidence in the robustness of these findings. Across all microbiome-targeted therapies, benefits were most consistently observed for GI outcomes, whereas improvements in core ASD symptoms were more variable and less predictable.

CONCLUSION: Microbiome-targeted therapies are a promising adjunctive strategy in managing children with ASD, especially for associated GI disorders. Probiotics and prebiotics provided the most reliable benefits for GI symptoms, while synbiotics may offer broader microbiome modulation, and FMT has the greatest observed improvements in both GI and behavioral outcomes. However, considerable heterogeneity across studies and limited high-quality randomized trials highlight the need for large, well-designed clinical trials with standardized intervention protocols to clarify clinical efficacy and guide future therapeutic recommendations.},
}

@article {pmid42962704,
year = {2026},
author = {May, L and Wolstenholme, J and Bajaj, J},
title = {Targeting the Microbiome to Treat Alcohol Use Disorder and Liver Disease.},
journal = {Seminars in liver disease},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2993-3789},
pmid = {42962704},
issn = {1098-8971},
abstract = {Alcohol use disorder and alcohol-associated liver disease represent a global health burden, yet treatment options remain limited. Emerging evidence has shown the intestinal microbiome to be a mediator of alcohol-associated organ injury, establishing gut dysbiosis, intestinal barrier dysfunction, and aberrant microbial metabolite production as drivers of disease. The gut-liver-brain axis provides a mechanistic framework in which microbial products and signals fuel hepatic inflammation, steatosis, fibrosis, and neuroinflammation that drive alcohol consumption. This review discusses current evidence on how chronic alcohol exposure shapes microbial communities, disrupts the gut epithelium, and alters innate immune and metabolic circuits in the liver and the brain. We examine how microbiome-targeted interventions, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, non-absorbable antibiotics, and short-chain fatty acid supplementation, can act on mechanistic targets along this axis. Finally, we highlight knowledge gaps, including the roles of causal microbial taxa, sex differences in gut-immune-brain signaling, and windows of reversibility that must be further investigated and understood to translate microbial modulation into effective therapies. In conclusion, this review summarizes the current literature on targeting the microbiome and the gut-liver-brain axis as a treatment approach, with a focus on the mechanisms within this axis and the interventions that target them.},
}

@article {pmid42963088,
year = {2026},
author = {Durr, KM and Hum, C and Kain, T and Tran, A and English, S and McIntyre, L},
title = {Randomised controlled trials of faecal microbiota transplantation in adult inpatients: a scoping review study protocol.},
journal = {BMJ open},
volume = {16},
number = {10},
pages = {e122741},
doi = {10.1136/bmjopen-2026-122741},
pmid = {42963088},
issn = {2044-6055},
}

@article {pmid42954768,
year = {2026},
author = {Debnath, D},
title = {The gut-ovary axis in polyendocrine metabolic ovarian syndrome: Mechanisms, microbiome dysbiosis, and emerging therapeutic strategies.},
journal = {International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijgo.71478},
pmid = {42954768},
issn = {1879-3479},
abstract = {Polycystic ovary syndrome (PCOS), recently termed polyendocrine metabolic ovarian syndrome (PMOS), is a heterogeneous endocrine-metabolic disorder characterized by reproductive, metabolic, and hormonal disturbances. Increasing evidence suggests that interactions between the gut microbiota and host physiology may be relevant to PMOS through pathways involving intestinal barrier function, inflammation, insulin sensitivity, steroid hormone metabolism, bile acid signaling, and gut-brain-ovary communication. This narrative review synthesizes current human and preclinical evidence on the gut-ovary axis in PMOS, with particular emphasis on microbial dysbiosis, proposed mechanistic pathways, microbiome-related metabolic and endocrine interactions, and emerging therapeutic approaches. Human studies generally report associations between altered microbial composition and metabolic or reproductive features of PMOS, although findings vary considerably according to population characteristics, bodyweight, diagnostic criteria, sequencing methods, and analytical approaches. Experimental studies provide additional support for potential roles of microbial metabolites, intestinal permeability, immune signaling, and metabolic pathways, but these mechanisms have not been established as causal in humans. Microbiome-targeted interventions, including probiotics, prebiotics, synbiotics, and dietary approaches, show potential, whereas fecal microbiota transplantation remains largely experimental. Conventional metabolic therapies, including glucagon-like peptide-1 receptor agonists, should be considered separately from microbiome-targeted approaches. Overall, the gut-ovary axis represents a promising framework for understanding the systemic features of PMOS, but substantial heterogeneity, limited longitudinal human evidence, and underrepresentation of diverse populations currently limit translation into clinical practice.},
}

@article {pmid42955203,
year = {2026},
author = {Sagawa, T and Hirakawa, M and Nagashima, H and Fujikawa, K},
title = {Gut Microbiome Signatures and Immune Checkpoint Inhibitor Response in Gastrointestinal Cancers: Reproducibility and Translational Readiness.},
journal = {Current oncology reports},
volume = {28},
number = {1},
pages = {},
pmid = {42955203},
issn = {1534-6269},
mesh = {Humans ; *Immune Checkpoint Inhibitors/therapeutic use ; *Gastrointestinal Neoplasms/drug therapy/microbiology/immunology ; *Gastrointestinal Microbiome/drug effects/immunology ; Reproducibility of Results ; Translational Research, Biomedical ; },
abstract = {PURPOSE OF REVIEW: Gut microbial features have been associated with immune checkpoint inhibitor (ICI) outcomes, but whether these signatures are robust across gastrointestinal (GI) tumor types, treatment regimens, and populations remains uncertain. This critical narrative review assesses human evidence, experimental mechanisms, longitudinal sampling, and the criteria needed for clinical implementation.

RECENT FINDINGS: A gastric cancer cohort showed different response-associated microbial features for immunotherapy alone, chemotherapy alone, and combined treatment. Cross-cancer strain-resolved analyses found that signature transportability was strongly conditional on matching ICI regimens. A large primary liver cancer cohort analyzed 315 patients and 777 serial samples and explored a baseline score derived from on-treatment species selection; later samples were available only in a selected subgroup, complicating interpretation. Experimental studies link selected microbes and metabolites with antitumor immunity, but these mechanistic findings do not establish therapeutic efficacy in humans. Fecal microbiota transplantation (FMT) studies in melanoma demonstrate feasibility yet do not establish benefit in GI malignancies. Stool profiles may not represent mucosal or tumor-adjacent communities in upper GI cancer. No stool microbiome signature is currently validated to select ICI therapy in GI oncology. Meaningful translation requires standardized assays, non-ICI comparators to establish treatment-effect prediction, strict separation of discovery and external validation, prospectively handled missingness, and randomized clinical-utility studies.},
}

Humans
*Immune Checkpoint Inhibitors/therapeutic use
*Gastrointestinal Neoplasms/drug therapy/microbiology/immunology
*Gastrointestinal Microbiome/drug effects/immunology
Reproducibility of Results
Translational Research, Biomedical

@article {pmid42957625,
year = {2026},
author = {Zi, Z and Liu, L and Zhou, J and Sun, Y and Wang, N and Liu, B and Liu, K and Tan, Y},
title = {Adolescent depression and gut microbiota dysbiosis: characteristics, mechanisms, and microbiota-targeted therapeutics.},
journal = {Translational psychiatry},
volume = {16},
number = {1},
pages = {},
pmid = {42957625},
issn = {2158-3188},
mesh = {Humans ; *Dysbiosis/microbiology/therapy/complications ; *Major Depressive Disorder/microbiology/therapy/physiopathology ; *Gastrointestinal Microbiome/physiology ; Adolescent ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics ; },
abstract = {Major depressive disorder (MDD) is one of the most prevalent mental disorders, yet its pathogenesis remains incompletely understood. Accumulating evidence indicates that MDD is closely associated with gut microbiota dysbiosis, with bidirectional communication along the microbiota-gut-brain axis playing a pivotal role in disease development. The gut microbiota and its metabolites exert dual influences on MDD, contributing to its pathophysiology while also offering promising therapeutic targets. In recent years, the prevalence of depression, especially in adolescents, has shown a sharp upward trend, increasing the risk of suicide in this population. However, few studies have systematically reviewed the link between gut dysbiosis and MDD in adolescents. This review summarizes current evidence on structural and functional alterations of the gut microbiota in adolescent MDD and explores the underlying mechanisms mediated by the microbiota-gut-brain axis. Furthermore, we also discuss the therapeutic potential of microbiota-targeted interventions, including dietary modification, probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Future research should aim to characterize specific microbial alterations in adolescent MDD and clarify the mechanisms underlying gut-brain interactions, thereby advancing the clinical translation of microbiota-targeted therapeutics for adolescent depression.},
}

Humans
*Dysbiosis/microbiology/therapy/complications
*Major Depressive Disorder/microbiology/therapy/physiopathology
*Gastrointestinal Microbiome/physiology
Adolescent
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Prebiotics

@article {pmid42957631,
year = {2026},
author = {Zhang, Z and Zhong, S and Gao, L and Chen, B and Huang, P},
title = {Gut microbiota-derived TNF-α triggers dopaminergic neuron ferroptosis via TNFR1-NF-κB-ATF4 axis in Parkinson's disease.},
journal = {Cell death discovery},
volume = {12},
number = {1},
pages = {},
pmid = {42957631},
issn = {2058-7716},
abstract = {Parkinson's disease (PD) pathogenesis remains incompletely understood, with the causal link between gut microbiota dysbiosis and central neurodegeneration unclarified. This study aimed to unravel this complex interplay by integrating Mendelian randomization (MR) analysis, animal models, cellular experiments, and transcriptomic profiling. MR analysis identified Clostridium sensu stricto 1 and Candidatus Soleaferrea as novel genetic risk factors for PD, providing causal evidence for gut microbiota-driven PD pathogenesis. Using a chronic MPTP-induced PD mouse model, we confirmed that gut microbiota dysbiosis is accompanied by elevated tumor necrosis factor-α (TNF-α) in the intestine, plasma, and midbrain, along with dopaminergic neuron loss and motor deficits. Fecal microbiota transplantation (FMT) from healthy mice reversed these phenotypes, restoring gut homeostasis, reducing TNF-α levels, and preserving dopaminergic neurons. Transcriptomic analysis of mouse midbrain and human PD substantia nigra (GEO datasets) revealed ferroptosis as a key enriched pathway, with activating transcription factor 4 (ATF4) significantly upregulated in both PD models and patients. Mechanistically, TNF-α induced ATF4 overexpression in a concentration- and time-dependent manner, triggering dopaminergic neuron ferroptosis. This effect was mediated by TNF-α binding to TNFR1 (not TNFR2), activating the NF-κB pathway, and subsequently upregulating ATF4. Knockdown of ATF4 or inhibition of NF-κB reversed TNF-α-induced ferroptosis, as evidenced by restored glutathione (GSH) levels, reduced malondialdehyde (MDA) accumulation, and improved cell viability. Our findings establish a novel gut-brain axis-mediated pathogenic pathway: gut microbiota dysbiosis drives TNF-α-TNFR1-NF-κB-ATF4 signaling, leading to dopaminergic neuron ferroptosis and PD progression. This study bridges the gap between peripheral microbial dysbiosis and central neurodegeneration, identifies potential therapeutic targets, and highlights FMT as a promising intervention for PD.},
}

@article {pmid42957852,
year = {2026},
author = {Gan, T and Rosen, AL and Wang, L and Vernon, S and Droit, L and Pinski, AN and Wu, G and Chica Cardenas, LA and Mihindukulasuriya, KA and Paredes, A and Pios, Z and Baldridge, MT and Rimmer, JE and Parkes, M and Dinsdale, EA and Edwards, RA and Segall, AM and Handley, SA and Kau, AL and Wang, D},
title = {A human gut-associated picobirnavirus establishes the Picobirnaviridae as the third clade of RNA bacteriophages.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
pmid = {42957852},
issn = {2058-5276},
support = {R01AI193051//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01AI165915//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; RC2DK116713//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; NIHR203312//DH | National Institute for Health Research (NIHR)/ ; },
abstract = {Picobirnaviruses (PBVs) are commonly detected RNA viruses in human and animal guts and are associated with multiple human diseases. Although PBVs have been assumed to infect vertebrate hosts, there is neither direct evidence for this nor any culture system to propagate PBVs. Here we demonstrate that a PBV infects bacteria and is therefore an RNA phage. Two different PBVs from human faeces were propagated in germ-free mice after faecal microbiota transplantation, establishing a mouse model for PBV. One PBV could be cultured in vitro, in a community of anaerobic gut bacteria, and its growth could be inhibited by multiple antibiotics. RNA fluorescence in situ hybridization revealed PBV RNA within bacterial cells, and enrichment and sequencing of PBV RNA-containing cells identified a previously unidentified 'Candidatus Anaerotignum faecalis' as its host. Our findings define the family Picobirnaviridae as only the third clade of RNA phages in addition to leviviruses and cystoviruses.},
}

@article {pmid42958990,
year = {2026},
author = {Ma, H and Chen, Y and Deng, X and Fang, X and Xiao, W and Long, Q and Du, L and Du, F and Chen, H and Wang, Y and Gao, B and Qiao, X},
title = {Morinda Officinalis Oligosaccharides Alleviate Post-Stroke Depression-Like Behaviors Alongside Increased Gut Microbial Diversity and Butyrate Levels and Reduced Hippocampal Pla2g4a Expression.},
journal = {CNS neuroscience & therapeutics},
volume = {32},
number = {11},
pages = {},
pmid = {42958990},
issn = {1755-5949},
support = {82204360//National Natural Science Foundation of China/ ; 7232348//Beijing Municipal Natural Science Foundation/ ; },
mesh = {Animals ; Male ; *Hippocampus/metabolism/drug effects ; Mice, Inbred C57BL ; *Depression/drug therapy/metabolism/etiology ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Oligosaccharides/therapeutic use/pharmacology/isolation & purification ; *Morinda ; *Butyrates/metabolism ; *Stroke/psychology/metabolism/complications ; Fecal Microbiota Transplantation ; },
abstract = {BACKGROUND AND PURPOSE: Post-stroke depression (PSD) represents a common and debilitating complication after cerebral ischemia, yet mechanism-based therapies remain an urgent unmet need. The microbiota-gut-brain axis has been implicated in PSD pathophysiology, but the precise molecular pathways are largely elusive. Morinda officinalis oligosaccharides (MOO), a clinically approved antidepressant in China, exhibit poor oral absorption, raising the possibility of a gut-dependent mechanism.

EXPERIMENTAL APPROACH: Male C57BL/6J mice were subjected to transient middle cerebral artery occlusion (MCAO) followed by 21 days of chronic restraint stress (CRS) to establish a PSD model. MOO (50 mg/kg/day) was administered via gavage from Day 7 to 27. Depression-like behaviors, 16S rRNA-based gut microbiota profiling, short-chain fatty acid (SCFA) quantification, intestinal and blood-brain barrier integrity assessments, and hippocampal proteomics were performed. The transferability of MOO-associated fecal effects was assessed using a donor-controlled fecal microbiota transplantation (FMT) design. The butyrate-Pla2g4a relationship was further examined by sodium butyrate supplementation and AAV-mediated hippocampal Pla2g4a overexpression.

KEY RESULTS: MOO administration altered gut microbial composition, increased the abundance of probiotics and decreased the abundance of harmful bacteria, and was accompanied by increased fecal butyrate levels. The donor-controlled FMT experiment provided preliminary evidence that fecally transferable factors from MOO-treated PSD donors may contribute to behavioral improvements in PSD recipients. MOO and sodium butyrate treatment were associated with improved indices of intestinal and blood-brain barrier integrity. Hippocampal proteomics identified Pla2g4a, a phospholipase linked to neuroinflammation, as a candidate molecule related to the observed effects. Both MOO and sodium butyrate treatment were associated with reduced hippocampal Pla2g4a expression, and Pla2g4a expression was inversely correlated with butyrate levels. Hippocampal Pla2g4a overexpression attenuated the behavioral improvements associated with sodium butyrate treatment, supporting the functional involvement of Pla2g4a in the response to sodium butyrate.

CONCLUSIONS AND IMPLICATIONS: MOO treatment was associated with improved depression-like behaviors in PSD mice, accompanied by gut microbial alterations, increased fecal butyrate, improved barrier integrity, and reduced hippocampal Pla2g4a expression. FMT findings provided preliminary evidence that fecally transferable factors from MOO-treated donors may contribute to behavioral improvements, while Pla2g4a overexpression attenuated the behavioral effects of sodium butyrate. These findings highlight a potential association among MOO, gut-derived butyrate, barrier integrity, and hippocampal Pla2g4a in PSD.},
}

Animals
Male
*Hippocampus/metabolism/drug effects
Mice, Inbred C57BL
*Depression/drug therapy/metabolism/etiology
*Gastrointestinal Microbiome/drug effects/physiology
Mice
*Oligosaccharides/therapeutic use/pharmacology/isolation & purification
*Morinda
*Butyrates/metabolism
*Stroke/psychology/metabolism/complications
Fecal Microbiota Transplantation

@article {pmid42959510,
year = {2026},
author = {Saheb, F},
title = {Post-COVID Gastrointestinal Symptoms and Disorders of Gut-Brain Interaction: A Focus on Persistent Diarrhea.},
journal = {Cureus},
volume = {18},
number = {9},
pages = {e117111},
pmid = {42959510},
issn = {2168-8184},
abstract = {Persistent gastrointestinal (GI) symptoms after SARS-CoV-2 infection include diarrhea, abdominal pain, dyspepsia, constipation, nausea, and other disorders of gut-brain interaction (DGBIs), but these entities should not be treated as interchangeable. In a meta-analysis of long-COVID studies, any GI symptom was reported in approximately 22% of patients and diarrhea in 10%, although heterogeneity was very high. In a large US Veterans Affairs cohort, post-acute COVID-19 was associated with incident diarrhea (hazard ratio {HR}:
1.58, 95% CI: 1.52-1.65; excess burden 7.99 per 1,000 persons at one year) and irritable bowel syndrome (HR: 1.54, 95% CI: 1.28-1.86). Prospective Rome IV cohorts report lower absolute rates of formally diagnosed DGBIs; one study found persistent DGBI symptoms in 6.6% at six months, with functional diarrhea in 2.2% and irritable bowel syndrome (IBS) in 2.5% at three months. Mechanistic evidence supports intestinal involvement during acute infection and demonstrates associations with epithelial/angiotensin-converting enzyme 2 (ACE2) perturbation, immune activation, barrier dysfunction, altered microbial taxa, and impaired microbial metabolite production. However, persistent viral RNA or antigen, dysbiosis, and gut-lung signaling remain proposed or associative mechanisms rather than established causes of chronic diarrhea. Treatment evidence specific to post-COVID functional diarrhea is sparse. A large synbiotic trial improved a broad "gastrointestinal upset" domain in post-acute COVID syndrome, but did not enroll a defined chronic diarrhea or Rome-positive population; probiotic and fecal microbiota transplantation trials showing GI effects were largely conducted during acute COVID-19. Therefore, current care should first exclude organic and medication-related causes, then apply phenotype-based management extrapolated from established diarrhea-predominant irritable bowel syndrome (IBS-D) and functional-diarrhea practice while clearly acknowledging the limited post-COVID-specific evidence. Standardized definitions, pre-infection GI data, appropriate controls, functional microbiome measures, and dedicated randomized trials are priorities for future research.},
}

@article {pmid42961005,
year = {2026},
author = {Li, M and Wang, B and Ma, Y},
title = {[Roles of growth factor-mediated brain-gut axis crosstalk in neurorepair following ischemic stroke].},
journal = {Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences},
volume = {},
number = {},
pages = {1-14},
doi = {10.3724/zdxbyxb-2026-0250},
pmid = {42961005},
issn = {1008-9292},
abstract = {In recent years, the brain-gut axis, a critical bidirectional signaling pathway between the central nervous system and the gut microbiota, has attracted increasing attention for its role in the pathological progression of ischemic stroke (IS). Cell growth factors, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF), are not only classical neuroprotective molecules but may also act as key signaling mediators of brain-gut axis communication because of their multifaceted roles in intestinal barrier regulation, peripheral immune remodeling, and central-peripheral crosstalk. Gut microbiota metabolites, such as short-chain fatty acids, tryptophan metabolites, and bile acid derivatives, can regulate BDNF, NGF, IGF-1, and VEGF through the PI3K/Akt and MAPK/ERK pathways, thereby affecting synaptic plasticity, neuronal survival, angiogenesis, and neural repair. The downstream signals of these factors converge on shared core pathways, producing functional additivity and synergistic effects. Based on these mechanisms, intervention strategies such as probiotic supplementation (e.g., Bifidobacterium bifidum), prebiotics or dietary fiber (e.g., inulin and arabinoxylan), natural product modulation (e.g., diosmetin, rhubarb extract, and cornuside), and fecal microbiota transplantation can reshape the gut microbiota, increase metabolites such as short-chain fatty acids, regulate tryptophan metabolism, and inhibit inflammatory pathways such as TLR4/NF-κB. These interventions indirectly upregulate endogenous growth factors, including BDNF, IGF-1, and FGF, and activate signaling pathways such as PI3K/Akt, MAPK/ERK, and BDNF/TrkB/CREB, thereby reducing cerebral infarct volume, improving neurological and cognitive function, alleviating post-stroke depression, and promoting hippocampal neurogenesis, thus demonstrating considerable neuroprotective potential. This review focuses on the interrelationships among cell growth factors, the brain-gut axis, and IS, explores how growth factors act as messengers of the brain-gut axis and play a bridging role in the pathological progression of IS, and discusses novel therapeutic strategies targeting this axis.},
}

@article {pmid42961559,
year = {2026},
author = {Gao, Y and Gao, X and Wang, K and Qiao, J and Jiang, C},
title = {The role of microbial enzymes in intervention strategies for metabolic diseases targeting the gut microbiota.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {42961559},
issn = {1869-1889},
abstract = {Metabolic diseases-including obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), type 2 diabetes mellitus (T2DM), atherosclerosis (AS), and polycystic ovary syndrome (PCOS)-pose a significant global health crisis due to their rapidly increasing prevalence. The therapeutic potential of the gut microbiota and its metabolites is gaining recognition, with microbial enzymes playing a pivotal role. These enzymes catabolize dietary fibers into mono- and oligo-saccharides, ultimately yielding beneficial short-chain fatty acids, while concurrently converting phytochemicals into absorbable, bioactive small molecules. An increasing array of small-molecule agonists and inhibitors has been developed to target microbial pathways, such as bile acid metabolism and trimethylamine formation. Furthermore, engineered bacteria and fecal microbiota transplantation are gaining traction as promising therapeutic strategies. This review synthesizes evidence on how microbial enzymes underpin these diverse interventions, aiming to advance the development of microbial enzyme-based management strategies for metabolic diseases.},
}

@article {pmid42950906,
year = {2026},
author = {Wan, D and Feng, X and Xu, S and Du, Q and Yue, W and Zhang, S},
title = {Siwu Paste alleviates blood deficiency syndrome induced by cyclophosphamide and acetylphenylhydrazine in association with gut microbiota remodeling and improved splenic metabolic homeostasis.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {122534},
doi = {10.1016/j.jep.2026.122534},
pmid = {42950906},
issn = {1872-7573},
abstract = {Siwu Paste (SWP), derived from the classical blood-tonifying formula Siwu Decoction, has long been used for blood deficiency-related disorders and has a well-established traditional basis and ethnopharmacological value. Blood deficiency syndrome (BDS) is a common syndrome in traditional Chinese medicine and is associated with impaired blood generation and hematopoietic dysfunction. However, the modern pharmacological mechanisms underlying the beneficial effects of SWP on BDS remain incompletely understood.

AIM OF THE STUDY: This study aims to evaluate the therapeutic effects of SWP on cyclophosphamide and acetylphenylhydrazine induced BDS and to investigate the potential mechanisms underlying its improvement of hematopoietic function.

METHODS: The chemical constituents of SWP were characterized by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and its potential mechanisms were predicted using network pharmacology. An acetylphenylhydrazine (APH)/cyclophosphamide (CTX)-induced BDS rat model was used to evaluate SWP efficacy through flow cytometry, histology, Western blotting, qPCR, 16S rRNA sequencing, and untargeted metabolomics. Broad-spectrum antibiotic treatment, fecal microbiota transplantation (FMT), and exogenous adenosine diphosphate (ADP) supplementation experiments were performed to evaluate the contribution of the gut microbiota and the involvement of splenic ADP-related metabolic alterations.

RESULTS: SWP significantly improved hematopoietic dysfunction, alleviated systemic inflammation, restored intestinal barrier integrity, reversed the Treg/Th17 imbalance, and reduced apoptosis within the CD45[+]CD34[+] bone marrow cell population in BDS rats. Multi-omics analysis revealed that SWP significantly regulated gut microbiota composition and metabolic profiles; specifically, SWP treatment was associated with a significant increase in the relative abundance of Allobaculum and an upward trend in Lactobacillus, accompanied by a significant reduction in the relative abundance of total ADP in spleen tissue compared with the BDS group. FMT experiments partially transferred the hematopoietic and immunomodulatory effects associated with SWP treatment. Broad-spectrum antibiotic treatment and exogenous ADP supplementation attenuated several SWP-induced improvements in bone-marrow hematopoietic function and Treg/Th17 balance, consistent with the involvement of the gut microbiota-splenic metabolic axis in the therapeutic effects of SWP.

CONCLUSION: SWP alleviates bone marrow hematopoietic dysfunction in BDS rats, with these effects accompanied by gut microbiota remodeling, restoration of intestinal barrier integrity, suppression of inflammation, and improved metabolic homeostasis. These findings provide modern pharmacological evidence supporting the traditional TCM concept of "treating the marrow via the gut" in blood deficiency-related disorders.},
}

@article {pmid42951052,
year = {2026},
author = {Ahangari, A and Tukmechi, A and Hadian, M and Mahmoudi, S and Babaei-Balderlou, F},
title = {Fecal microbiota transplantation and its role in aging of rats: Behavioral and pathological evidence.},
journal = {Experimental gerontology},
volume = {},
number = {},
pages = {113371},
doi = {10.1016/j.exger.2026.113371},
pmid = {42951052},
issn = {1873-6815},
abstract = {Aging is associated with progressive oxidative stress, chronic inflammation and functional deterioration across multiple organs. Increasing evidence suggests that the gut microbiota plays a pivotal role in regulating aging through the gut-brain axis and systemic immune interactions. The present study investigated the therapeutic potential of fecal microbiota transplantation (FMT) in a D-galactose-induced rat model of accelerated aging. Male rats were allocated into four experimental groups: Healthy control, D-galactose-induced aging, aging treated with FMT and aging treated with antibiotics prior to FMT. Accelerated aging was induced by intraperitoneal administration of D-galactose (150 mg/kg/day). FMT was performed using fecal microbiota obtained from healthy donor rats. Cognitive performance was assessed using the Morris Water Maze (MWM), and histopathological alterations were evaluated in the heart, hippocampus and colon using hematoxylin and eosin staining. D-galactose administration significantly impaired spatial learning and memory and induced marked pathological alterations, including myocardial edema and hemorrhage, neuronal degeneration and vacuolation in the hippocampus, and crypt disruption with inflammatory cell infiltration in the colon. FMT markedly improved behavioral performance and substantially attenuated tissue damage in all examined organs. In contrast, antibiotic pretreatment was associated with less pronounced improvement following FMT, suggesting that the recipient intestinal environment may influence the response to transplantation. These findings provide behavioral and histopathological evidence consistent with beneficial effects of FMT on several features of accelerated aging; however, direct changes in microbial composition, microbial function, and donor engraftment were not assessed.},
}

@article {pmid42952078,
year = {2026},
author = {Kwok, SL and Xiao, YC and Cai, XB},
title = {Fecal Microbiota Transplantation: A Promising Therapeutic Strategy Targeting the Microbiota-Gut-Brain Axis in Anorexia Nervosa.},
journal = {Brain and behavior},
volume = {16},
number = {11},
pages = {},
pmid = {42952078},
issn = {2162-3279},
support = {2023//The "Talents Support" Program of the First Affiliated Hospital of Shantou University Medical College/ ; 2024//Wu Jieping Medical Foundation Special Research Funding/ ; },
mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Anorexia Nervosa/therapy/microbiology ; Animals ; *Gastrointestinal Microbiome/physiology ; *Brain-Gut Axis/physiology ; *Brain ; },
abstract = {PURPOSE: Anorexia nervosa (AN) is a complex psychiatric disorder characterized by self-starvation, body-image disturbance, and serious medical complications. Because current treatments have variable outcomes and relapse is common, the microbiota-gut-brain axis has been investigated as a possible contributor to disease persistence. This review evaluates fecal microbiota transplantation (FMT) as an experimental microbiota-directed strategy for AN.

METHODS: PubMed, Embase, Scopus, and Google Scholar were searched for relevant studies published from January 1990 to October 2025. Eligible evidence included human reports, animal studies, and mechanistic studies examining FMT or gut-microbiota alterations in AN and related pathways.

FINDINGS: Individuals with AN have been reported to show altered microbial diversity and changes in taxa associated with short-chain fatty acid production and inflammation. These findings are heterogeneous and may reflect starvation, diet, medication exposure, or illness-related physiology. Human evidence for FMT in AN is limited to small, uncontrolled studies and case reports, while most mechanistic support comes from animal models or indirect evidence from other conditions.

CONCLUSION: Evidence for FMT in AN remains preliminary and is largely based on uncontrolled human observations and preclinical studies. FMT may alter gut microbial composition and gastrointestinal or metabolic measures, but controlled efficacy data are absent and psychiatric benefits remain unconfirmed. Well-designed controlled trials are needed to establish its safety and clinical efficacy.},
}

*Fecal Microbiota Transplantation/methods
Humans
*Anorexia Nervosa/therapy/microbiology
Animals
*Gastrointestinal Microbiome/physiology
*Brain-Gut Axis/physiology
*Brain

@article {pmid42953133,
year = {2026},
author = {Gao, S and Zhuang, J and Cheng, H and Hu, K and Zhuang, L and Pan, Y},
title = {Gut-liver axis dysregulation and restoration in decompensated hepatitis B cirrhosis: rationale and research progress of fecal microbiota transplantation.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1949414},
pmid = {42953133},
issn = {1664-302X},
abstract = {Decompensated hepatitis B virus (HBV) related cirrhosis is associated with high mortality and a wide range of complications. Current antiviral and symptomatic treatments fail to reverse core pathological alterations, including disruption of the gut microbial ecosystem. Gut-liver axis imbalance represents a central hub in disease progression. Gut dysbiosis compromises the intestinal mucosal barrier, leading to endotoxin translocation into the bloodstream, which in turn exacerbates hepatic inflammation and fibrosis, thereby establishing a vicious cycle. This review synthesizes the key mechanisms, clinical efficacy, administration routes, and safety profile of fecal microbiota transplantation (FMT) in this disease. It also identifies current technical bottlenecks and research gaps in FMT application and discusses future directions toward precision based and standardized clinical translation of this therapeutic approach.},
}

@article {pmid42954409,
year = {2026},
author = {Yi, L and Yuan, Y and Ma, X and Li, C and Hao, Y and Ma, Q and Liu, X and Du, X and Shao, L and Wang, S and Xu, J},
title = {Disease-specific gut microbiota-metabolite-immune networks in hematologic disorders: mechanisms, causal support, and translational strategies.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2752469},
doi = {10.1080/19490976.2026.2752469},
pmid = {42954409},
issn = {1949-0984},
mesh = {Humans ; *Hematologic Diseases/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/microbiology/immunology ; Animals ; Host Microbial Interactions/immunology ; Hematopoietic Stem Cell Transplantation ; },
abstract = {The gut microbiota is increasingly recognized as a systemic regulator of host immunity, host metabolism, epithelial barrier integrity, and distal tissue homeostasis. Hematologic disorders provide an important setting in which these host-microbe interactions converge on immune remodeling, marrow-niche function, hematopoietic recovery, treatment response, and transplant-related complications. This narrative review synthesizes mechanistic, clinical, and translational evidence linking gut microbial dysbiosis to benign and malignant hematologic diseases, clonal and premalignant states, and hematopoietic stem cell transplantation (HSCT)-related outcomes. Rather than treating microbiome associations as a single evidence category, we distinguish five complementary evidence strata: Mendelian randomization, experimental models, prospective human cohorts, randomized human interventions, and cross-sectional studies. These study designs address different causal questions and are interpreted as complementary rather than as a single linear hierarchy. We also separate microbial composition from microbial function: taxon-level enrichment or depletion is treated primarily as context-dependent and hypothesis-generating, whereas conserved functional pathways-including short-chain fatty acids, bile-acid transformation, tryptophan metabolism, microbial translocation and barrier dysfunction, and innate immune activation-provide the principal cross-disease mechanistic framework. We integrate disease-specific microbial features, functional mediators, immune and marrow consequences, and clinical outcomes into an author-constructed evidence map, while explicitly addressing bidirectionality, reverse causality, and translational readiness. Emerging applications include microbiota-based biomarkers, treatment-response prediction, fecal microbiota transplantation, probiotics and postbiotics, antibiotic stewardship, and microbiota-dependent modulation of drug metabolism.},
}

Humans
*Hematologic Diseases/microbiology/immunology/therapy
*Gastrointestinal Microbiome/immunology
*Dysbiosis/microbiology/immunology
Animals
Host Microbial Interactions/immunology
Hematopoietic Stem Cell Transplantation

@article {pmid42619328,
year = {2026},
author = {Fisher, BT and Blumenstock, JA and Boge, CLK and Shuster, S and Seif, AE and Green, M and Michaels, MG and Alexander, JL and Ardura, MI and Auletta, JJ and Miller, TP and Hijano, DR and Muller, WJ and Schuster, JE and Green, AM and Dulek, DE and Li, Y and Kajon, AE and Grimley, M and Danziger-Isakov, L},
title = {Incidence and Outcomes of Human Adenovirus Infection and Disease in a Multicenter Cohort of Pediatric Allogeneic Hematopoietic Cell Transplant Recipients.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {83},
number = {4},
pages = {e858-e866},
doi = {10.1093/cid/ciag398},
pmid = {42619328},
issn = {1537-6591},
support = {//National Institute for Allergy and Infectious Diseases/ ; /FD/FDA HHS/United States ; /FD/FDA HHS/United States ; },
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Child ; Female ; Child, Preschool ; Incidence ; Infant ; Transplantation, Homologous/adverse effects ; Adolescent ; *Adenovirus Infections, Human/epidemiology/mortality/virology ; *Adenoviruses, Human/isolation & purification/genetics ; *Transplant Recipients ; Feces/virology ; Cohort Studies ; DNA, Viral/blood ; Polymerase Chain Reaction ; },
abstract = {BACKGROUND: Human adenovirus (HAdV) among pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients can result in asymptomatic infection with risk for disease progression. There are limited data defining HAdV infection, disease, and case-fatality rates in a HAdV polymerase chain reaction (PCR) surveillance testing era. The current study aimed to define these outcomes using a priori definitions applied by a central review committee.

METHODS: Pediatric allo-HCT recipients were followed up for 180 days after HCT at 10 pediatric institutions. Blood and stool specimens were collected 0-7 days prior to allo-HCT for serum HAdV immunoglobulin G and stool HAdV PCR testing. Clinical data, including HAdV PCR testing results, informed central review committee-designated outcomes of HAdV infection, including DNAemia, disease, and deaths (case-fatality rate). Outcomes were reported by HAdV surveillance testing status and by pretransplant research specimen results.

RESULTS: The cohort included 819 allo-HCT recipients; 649 (79.2%) were under HAdV surveillance. The HAdV infection and DNAemia incidence among surveilled patients was 27.1% and 16.0%, respectively. The incidence of proven or probable HAdV disease was 10.9% for the cohort and, 12.6% for those under surveillance. The HAdV infection incidence was highest (13 of 25 [52.0%]) in patients with pre-HCT HAdV immunoglobulin G and stool PCR positivity. The attributable case-fatality rate for those with proven or probable disease was 13.5%.

CONCLUSIONS: HAdV infection and disease are common among pediatric allo-HCT recipients. HAdV disease is associated with a substantial HAdV-attributable mortality rate. Clinical trials assessing novel HAdV in pediatric allo-HCT recipients are needed. Pretransplant serology and stool PCR testing could identify high-risk patients for trial enrollment.},
}

Humans
*Hematopoietic Stem Cell Transplantation/adverse effects
Male
Child
Female
Child, Preschool
Incidence
Infant
Transplantation, Homologous/adverse effects
Adolescent
*Adenovirus Infections, Human/epidemiology/mortality/virology
*Adenoviruses, Human/isolation & purification/genetics
*Transplant Recipients
Feces/virology
Cohort Studies
DNA, Viral/blood
Polymerase Chain Reaction

@article {pmid42944171,
year = {2026},
author = {Zhang, T and Zhang, Y and Zhang, M and Liu, J and Zhang, Y and Feng, Y and Han, W and Zhu, Z and Chen, H and Huang, X},
title = {Study on Intestinal Adaptation Mechanism of Sika Deer to High-Tannin Diet and the Mediating Role of Gut Microbiota.},
journal = {Veterinary sciences},
volume = {13},
number = {10},
pages = {},
pmid = {42944171},
issn = {2306-7381},
support = {3236130287//National Natural Science Foundation of China/ ; },
abstract = {Tannins are plant-derived polyphenolic anti-nutritional factors that impair nutrient absorption, damage the intestinal barrier, and disrupt metabolic homeostasis. Some animals, however, have an innate resistance to the effects of tannins. Sika deer (Cervus nippon) exhibit strong tolerance to long-term consumption of tannin-rich oak plants, and Akkermansia muciniphila is considered a key functional bacterium, yet the underlying mechanism of this remains unclear. In this study, we transplanted fecal microbiota from tannin-acclimated sika deer into antibiotic-pretreated C57BL/6J mice, followed by tannin gavage to establish a stress model. Growth performance, serum glycolipid indices, and hepatic metabolic gene and protein expression were detected. Results showed no significant differences in body weight, fat deposition, or serum biochemical parameters between groups. In the transplantation group, key genes involved in glycolysis, detoxification, and lipid metabolism were significantly upregulated, while CYP7A1, a bile acid synthesis rate-limiting gene, was significantly downregulated at both transcriptional and protein levels. Akkermansia was specifically enriched in the gut of transplanted mice. In conclusion, the microbiota of the sika deer gut alleviates tannin toxicity and enhances host tolerance by regulating hepatic glycolipid and bile acid metabolism pathways. The results of our study provide new insights into the adaptation mechanisms of herbivores to high-tannin diets.},
}

@article {pmid42944643,
year = {2026},
author = {Yang, D and Zhu, L and Chen, J and Zhao, H and Chen, Y and Pan, S and Li, N and Chen, D},
title = {A Synergistic Hydrogel Strategy for the Treatment of Candida Vaginitis Through Pathogen Clearance and Microecosystem Restoration.},
journal = {Advanced materials (Deerfield Beach, Fla.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/adma.75465},
pmid = {42944643},
issn = {1521-4095},
support = {82670765//National Natural Science Foundation of China/ ; LQN25B030009//Zhejiang Provincial Natural Science Foundation of China/ ; 2024GR024//Industry-University-Research Innovation Fund for Chinese Universities-Infection and Control Project/ ; //Zhejiang Provincial Major Research and Development Project/ ; 2025C02135//New Technology Research on Microencapsulated Fecal Microbiota Transplantation for the Treatment of Autoimmune Liver Disease Based on Targeted Delivery/ ; KYZD202201//Basic Scientific Research Funds of Department of Education of Zhejiang Province/ ; 2024CXZD02//Hangzhou Medical College Scientific and Technological Innovation Guidance Fund/ ; WIUCASQD2023026//startup funding from Wenzhou Institute of UCAS/ ; WIUCASQD2021043//startup funding from Wenzhou Institute of UCAS/ ; Y20240088//Science and Technology Plan Project of Wenzhou Municipality/ ; },
abstract = {Microbial infections often disrupt the delicate balance of host commensal microbiota, leading to dysbiosis and recurrent infections, yet current therapies lack the capacity to simultaneously eradicate pathogens and restore ecological homeostasis. Here, we report a synergistic therapeutic strategy for Candida vaginitis that integrates targeted pathogen clearance with vaginal microecosystem restoration. We engineer a vaginal microenvironment-degradable hydrogel, HCS/FUC@Lab[PC], which self-assembles from highly deacetylated high molecular-weight chitosan oligosaccharide (HCS) and fucoidan (FUC) to encapsulate Lactobacillus (Lab) coated with procyanidine (PC). Within the vaginal microenvironment, the hydrogel gradually degrades and releases HCS, which efficiently eliminates Candida albicans (C. albicans) by disrupting cell wall integrity and interfering MAPK related signaling. FUC and PC further contribute to microenvironmental remodeling through their intrinsic anti-inflammatory and antioxidant activities. This remodeling facilitates stable colonization of Lab, which subsequently reinforces barrier integrity through competitive exclusion and metabolic modulation. In murine models, this approach effectively disrupts the infection-dysbiosis-recurrence vicious cycle, supporting an integrated therapeutic strategy that combines pathogen clearance, microenvironmental remodeling, and microecosystem restoration.},
}

@article {pmid42946830,
year = {2026},
author = {Leake, I},
title = {Limited efficacy of faecal microbiota transplantation in IBS.},
journal = {Nature reviews. Gastroenterology & hepatology},
volume = {},
number = {},
pages = {},
pmid = {42946830},
issn = {1759-5053},
}

@article {pmid42946849,
year = {2026},
author = {Ran, W and Wu, X and Liu, D and Lu, L and Yao, Y and Yang, M and Hou, F and Gong, Q and Gao, J},
title = {The gut microbiota-IPA axis mediated by catalpol alleviates DSS-induced colitis through AhR activation.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42946849},
issn = {1432-1912},
support = {YJSKYJJ2025011//Scientific Research Fund of Graduate of Zunyi Medical University/ ; [2025]043//Guizhou Provincial Major Scientific and Technological Program/ ; (2025)030//Guizhou Provincial Department of Science and Technology 2025 Central Government-Guided Local Science and Technology Development Fund Project/ ; No. GCC [2023]042//"hundred" level of high-level innovative talents in Guizhou Province/ ; },
abstract = {Current management strategies for colitis predominantly involve broad immunosuppression, underscoring the urgent need for strategies that restore essential homeostatic pathways. Insufficient activation of the aryl hydrocarbon receptor (AhR) by microbial metabolites compromises its crucial role in maintaining mucosal integrity, a defect commonly observed in colitis. While the natural compound catalpol exhibits preventive potential, its precise function within host-microbiota crosstalk remained undefined. This study aims to investigate the protective effects of catalpol on colitis, focusing on the role of gut microbiota and its metabolite, indole-3-propionic acid (IPA). A mouse model of DSS-induced colitis was utilized. The protective outcomes and mechanisms were assessed through integrated multi-omics analyses, functional validation via microbial manipulation, and molecular studies confirming the activation of the AhR pathway. In this study, catalpol protects against DSS-induced colitis in mice, and this protection is associated with alterations in gut microbiota composition. Integrated multi-omics analysis suggests that catalpol treatment is associated with increased relative abundance of Lachnospiraceae at the family level and with elevated levels of the microbial metabolite indole-3-propionic acid. Functional validation through fecal microbiota transplantation from catalpol-treated mice or direct IPA supplementation partially reproduced several protective effects, suggesting that IPA may be a downstream mediator contributing to the protective effects of catalpol. Molecular analyses indicate that both catalpol and IPA can physically interact with AhR. Importantly, pharmacological suppression of AhR partially reversed the protective effects, suggesting that AhR activation contributes to the protective effects of catalpol. Collectively, these findings suggest that catalpol protects against DSS-induced colitis, and this effect is associated with increased relative abundance of Lachnospiraceae at the family level and elevated IPA levels, potentially contributing to a microbiota-IPA-AhR axis. This work highlights the preventive potential of restoring host-microbiota metabolic crosstalk and provides a rationale for developing microbiota-targeted protective strategies.},
}

@article {pmid42947250,
year = {2026},
author = {Kronsten, VT and Ntuli, Y and Paintsil, EK and Woodhouse, CA and Tranah, TH and Cheung, S and Hagan, D and Merrick, B and Cape, A and Maher, F and Sultana, K and Prossomariti, D and Rodrigues, S and Masterson, C and Hebditch, V and Zamalloa, A and Mullish, BH and Singanayagam, A and Patel, VC and Thursz, MR and , and Goldenberg, SD and Carter, B and Edwards, LA and Shawcross, DL},
title = {PROMISE: a PROspective randomised double-blind parallel group placebo-controlled multicentre trial of faecal MIcrobiota tranSplantation to improve outcomEs in patients with cirrhosis over 24 months-study protocol for a clinical trial.},
journal = {Trials},
volume = {27},
number = {1},
pages = {},
pmid = {42947250},
issn = {1745-6215},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; Double-Blind Method ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; *Liver Cirrhosis/therapy/microbiology ; Prospective Studies ; *Gastrointestinal Microbiome ; Time Factors ; Clinical Trials, Phase III as Topic ; },
abstract = {BACKGROUND: Patients with cirrhosis have reduced gut bacterial diversity and a gut microbiota dominated by pathobionts. These changes, coupled with increased gut permeability and bacterial translocation, increase susceptibility to infection and death. There is also considerable concern that high antimicrobial exposure in the cirrhotic population drives the development of antimicrobial resistance (AMR). We previously performed a randomised feasibility trial of endoscopically administered jejunal faecal microbiota transplant (FMT) slurry derived from stringently screened donors, and showed it to be safe and well-tolerated in patients with cirrhosis (PROFIT Trial: NCT02862249). FMT was associated with reduced enteropathogenic bacteria in the gut, augmented ammonia excretion, ameliorated systemic inflammation, and enhanced innate immune responses to pathogen challenge. The trial was not powered to detect differences in clinical outcomes. The PROMISE study will evaluate the efficacy of lyophilised encapsulated FMT to reduce infection, decompensating events and mortality in patients with cirrhosis secondary to alcohol-related liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis and metabolic dysfunction and alcohol-related liver disease (MetALD).

METHODS: The PROMISE study is a phase 3 multicentre, randomised, double-blinded, placebo-controlled trial that will evaluate encapsulated lyophilised FMT in 300 participants with ALD, MetALD or MASLD cirrhosis (Model for End-Stage Liver Disease Sodium (MELD-Na) score 8-16). Participants will be randomly allocated (1:1) to receive FMT or matched placebo capsules every 91 days for 21 months, with 24-month follow-up. The primary endpoint is time-to-infection or decompensating event resulting in presentation to the emergency department or hospitalisation. Secondary endpoints include all hepatic decompensation, all-cause infection, antibiotic usage, incidence of AMR, hospitalisation rates, liver disease severity scores, quality of life scores, Hospital Anxiety and Depression Scale score (HADS), alcohol use, and mortality. Mechanistic endpoints include quantification of plasma bacterial DNA, plasma and faecal cytokines/biomarkers, plasma and faecal metabolome, faecal proteome, faecal microbiome composition and diversity (including resistome) and monocyte and mucosal-associated invariant T (MAIT) cell frequency, phenotype and function. Recruitment commenced in June 2023. Results will be disseminated via peer-reviewed journals, international conferences and patient support groups.

DISCUSSION: The PROMISE study will assess the efficacy and evaluate the mechanisms of action of FMT in patients with ALD, MASLD and MetALD cirrhosis. FMT may provide an alternative non-antibiotic treatment for these patients through ecological reconstitution of microbial balance.

TRIAL REGISTRATION: ISRCTN, ISRCTN17863382. Registered on 25th March 2022, https://www.isrctn.com/ISRCTNISRCTN17863382 .

CLINICALTRIALS: gov NCT06461208. Registered on 4th June 2024, https://clinicaltrials.gov/study/NCT06461208#study-overview .},
}

Humans
*Fecal Microbiota Transplantation/methods/adverse effects
Double-Blind Method
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Treatment Outcome
*Liver Cirrhosis/therapy/microbiology
Prospective Studies
*Gastrointestinal Microbiome
Time Factors
Clinical Trials, Phase III as Topic

@article {pmid42947729,
year = {2026},
author = {Tong, A and Zheng, Y and Cheng, W and Wu, J and Zheng, Y and Liu, S and Liu, X and Zhao, C and Liu, B},
title = {Low-glycemic index functional flour modulates gut microbiota in association with anti-obesity effects in mice.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1910403},
pmid = {42947729},
issn = {2296-861X},
abstract = {BACKGROUND: Obesity has become a prevalent global chronic disease, and dietary intervention is a safe and effective strategy for obesity prevention and management. Laminaria japonica and Lentinula edodes are widely consumed edible resources in China, while the lipid-lowering efficacy of functional noodles supplemented with their dietary fibers remains unclear. Moreover, the potential synergistic effects of combining these fibers with other functional plant ingredients have not been systematically explored.

METHODS: This study developed three low-glycemic index (low-GI) functional flour formulations (R1: basic formula; R2: basic formula supplemented with L. japonica and L. edodes dietary fibers; R3: R2 fortified with additional functional starches) based on nutritional balance principles. The in vitro nutritional properties, digestibility, cholesterol and bile salt binding capacities, as well as α-glucosidase and pancreatic lipase inhibitory activities were evaluated. Furthermore, a high-fat diet-induced obese ICR mouse model was established to evaluate the in vivo regulatory effects of the three formulations via a 6-week dietary intervention.

RESULTS: All three formulations exhibited GI values below 55 and showed significantly lower starch hydrolysis rates compared with wheat flour (WF), along with enhanced cholesterol adsorption capacity and bile salt-binding capacities, as well as stronger α-glucosidase and pancreatic lipase inhibitory activities. In the animal experiments, all three formulations significantly reduced mouse body weight, alleviated liver damage and hepatocellular pathology, reduced epididymal adipocyte size, and attenuated cecal tissue inflammation, with R3 showing the most pronounced effects. Notably, Formula 3 (R3) treatment also significantly modulated gut microbiota composition, as evidenced by increased beneficial bacteria, a reduced Firmicutes/Bacteroidetes (F/B) ratio, decreased potentially pathogenic taxa, and elevated fecal short-chain fatty acids (acetic, propionic, butyric, and isobutyric acids) compared with the model group. Correlation analyses revealed significant associations between specific microbial genera and metabolic parameters.

CONCLUSION: These findings suggest that the low-GI functional flours, particularly R3, improve metabolic health in obese mice, accompanied by modulation of gut microbiota and short-chain fatty acids (SCFAs) production. However, given the correlational nature of the current data, causal relationships need to be confirmed through further mechanistic studies, such as fecal microbiota transplantation. Overall, R3 represents a promising dietary intervention for obesity management.},
}

@article {pmid42947762,
year = {2026},
author = {Tang, Z and Chen, J and Peng, D and Mo, B and Yao, S and Xie, H and Jiang, D and Zhuo, W and Zhang, H and Zhou, Z},
title = {Combined fecal microbiota transplantation and adipose-derived stem cells protect the blood-spinal cord barrier after spinal cord injury.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1877863},
pmid = {42947762},
issn = {1664-3224},
mesh = {Animals ; *Spinal Cord Injuries/therapy/pathology/metabolism ; *Blood-Spinal Cord Barrier/metabolism ; *Fecal Microbiota Transplantation/methods ; Mice ; Humans ; Mice, Inbred C57BL ; Disease Models, Animal ; Recovery of Function ; *Stem Cell Transplantation ; Female ; Combined Modality Therapy ; },
abstract = {BACKGROUND: Blood-spinal cord barrier (BSCB) disruption and neuroinflammation contribute to secondary injury after spinal cord injury (SCI). Fecal microbiota transplantation (FMT) and human adipose-derived stem cells (hADSCs) each show therapeutic potential, but the effects of combined treatment and the influence of fecal soluble components on hADSCs secretory activity remain unclear.

METHODS: A T9 forceps-crush SCI model was established in C57BL/6J mice to compare FMT, intralesional hADSCs transplantation, and their combination. Functional recovery, BSCB permeability, neuroinflammation, lesion pathology, and neural tissue preservation were evaluated. Exploratory 16S rRNA sequencing was performed at 35 days post-injury. In vitro, hADSCs were exposed to filtered fecal material from healthy donor mice, and their conditioned medium was applied to oxygen-glucose deprivation/reoxygenation-injured bEnd.3 endothelial cells.

RESULTS: Combined FMT and hADSCs treatment improved locomotor recovery, attenuated BSCB leakage and neuroinflammatory responses, and preserved neural tissue, with several outcomes greater than either monotherapy. Exploratory 16S analysis identified treatment-associated differences in microbial richness and overall community composition. Fecal-filtrate preconditioning increased hADSCs secretion of VEGF, HGF, and IL-10 by 2.3-, 2.2-, and 1.8-fold, respectively. Conditioned medium from preconditioned hADSCs improved wound closure, preserved ZO-1 and Claudin-5 signals, and reduced endothelial monolayer permeability after OGD/R. IL-10 silencing partially attenuated these protective effects.

CONCLUSIONS: Combined FMT and hADSCs treatment was associated with greater BSCB preservation, reduced neuroinflammation, and improved functional recovery after SCI. In vitro, soluble components of healthy-donor fecal filtrate modulated hADSCs secretory activity and enhanced endothelial protection. These findings do not establish that oral FMT reprograms transplanted hADSCs in vivo or that microbiota alterations mediate the combined therapeutic effect.},
}

Animals
*Spinal Cord Injuries/therapy/pathology/metabolism
*Blood-Spinal Cord Barrier/metabolism
*Fecal Microbiota Transplantation/methods
Mice
Humans
Mice, Inbred C57BL
Disease Models, Animal
Recovery of Function
*Stem Cell Transplantation
Female
Combined Modality Therapy

@article {pmid42947989,
year = {2026},
author = {Sallem, OK},
title = {Phenotype-informed selection of microbiota-directed interventions in irritable bowel syndrome: current evidence and limitations.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1921349},
pmid = {42947989},
issn = {1663-9812},
abstract = {Irritable bowel syndrome (IBS) is a heterogeneous disorder of gut-brain interaction in which bowel-habit subtype, dominant symptoms, post-infectious onset, bile-acid handling, visceral sensitivity, and diet-microbiota interactions may influence the treatment response. This narrative mini-review asks whether available clinical evidence is sufficient to select or sequence microbiota-directed and microbiota-modulating interventions according to Rome bowel-habit subtype and clinically observable dominant symptoms. Literature was identified through PubMed/MEDLINE and major guidelines, systematic reviews, meta-analyses, and pivotal trials published through June 2026. Evidence was interpreted at the level of the exact intervention or product, studied population, target outcome, consistency, independent replication, safety, and guideline position. Mechanistic data support plausible links through fermentation, epithelial barrier function, mucosal immunity, bile-acid metabolism, visceral sensitivity, and gut-brain signaling, but mechanistic or microbiome changes do not establish the clinical efficacy. Rifaximin has the clearest replicated and guideline-supported role in IBS with diarrhea, while soluble fiber has guideline support for global or constipation-associated symptoms. Evidence for individual probiotics, postbiotics, partially hydrolyzed guar gum, galactooligosaccharides, and fermented matrices remains product-specific or emerging and is rarely independently replicated. Symptom improvement with a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (low-FODMAP diet) does not establish microbiota mediation. Fecal microbiota transplantation (FMT) and microbiome-guided prescribing remain investigational. Current evidence, therefore, supports only limited phenotype-informed matching and does not establish a validated treatment sequence or microbiome-defined therapeutic phenotype.},
}

@article {pmid42948400,
year = {2026},
author = {Yu, Y and Wang, J and Yuan, Q and Yu, L and Zhang, C},
title = {Evaluating traditional Chinese medicine modulation of the gut microbiota-bile acid axis in metabolic and inflammatory diseases: mechanistic evidence and translational priorities.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1977691},
pmid = {42948400},
issn = {1664-302X},
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, type 2 diabetes mellitus (T2D), and inflammatory bowel disease (IBD) are clinically distinct disorders that share perturbations in intestinal ecology, bile-acid composition, epithelial barrier function, and immune-metabolic regulation. Traditional Chinese medicine (TCM) may modify these interconnected processes, but the translational significance of reported effects remains uncertain. Changes in microbial composition are often interpreted as mechanisms without evidence of altered microbial function, bile-acid profiles or concentrations, receptor engagement, or clinical benefit. Here, we present a structured narrative review that uses the gut microbiota-bile acid axis to evaluate TCM in metabolic and inflammatory disease. We describe how microbial bile salt hydrolases, the bile acid-inducible (bai) operon, hydroxysteroid dehydrogenases, and amino-acid conjugation diversify the bile-acid pool and influence farnesoid X receptor (FXR), Takeda G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5), and immune pathways. We then assess evidence for defined TCM constituents and formulae in MASLD, obesity/T2D, and IBD. Across these settings, the most informative studies combine a standardized intervention with longitudinal metagenomic and targeted bile-acid profiling, host-signaling measurements, and an outcome that is attenuated by microbiota depletion, fecal microbiota transplantation, or functional microbial manipulation. Only one eligible human trial, of Qushi Huayu in adults enrolled under the historical NAFLD designation, reported both clinical and microbiota-related outcomes. Evidence for obesity/T2D and IBD was predominantly preclinical or observational, and the framework is therefore a translational assessment tool rather than a clinically validated model. We therefore propose an evidence hierarchy and a minimum translational package that integrates chemical quality control, dietary and co-medication assessment, strain- and gene-resolved microbiome analysis, targeted bile-acid metabolomics, and pathway-directed validation. TCM should be considered a potential precision adjunct to standard care only when reproducible microbial-metabolic phenotypes are linked to clinically meaningful benefit.},
}

@article {pmid42948641,
year = {2027},
author = {Rossetti, C and Aeschlimann, L and Praz, L and Boutrel, B},
title = {The gut-brain axis in Binge Eating Disorder: From microbial dysbiosis to vagal dysfunction and therapeutic intervention.},
journal = {Gut microbes reports},
volume = {4},
number = {1},
pages = {2749978},
pmid = {42948641},
issn = {2993-3935},
abstract = {Binge Eating Disorder (BED), the most prevalent eating disorder worldwide, is characterized by recurrent episodes of uncontrolled food intake accompanied by marked psychological distress in the absence of regular compensatory behaviors. While behavioral and neurobiological frameworks have traditionally dominated research, converging evidence now positions the gut microbiota as a critical mediator of BED pathophysiology through bidirectional microbiota-gut-brain axis (MGBA) communication. This review synthesizes current knowledge of gut microbial remodeling in BED, elucidating how compositional alterations contribute to pathogenesis through disrupted satiety signaling, altered neurotransmitter metabolism, immune-inflammatory cascades, and vagal dysfunction. Recent evidence highlights BED-specific depletion of fermentative taxa, including Pediococcus, Catenibacterium, and Megasphaera, with depletion of Pediococcus correlated with reduced cardiac vagal tone. The mechanistic landscape encompasses short-chain fatty acid (SCFA)-mediated appetite modulation, α-MSH mimicry by bacterial caseinolytic protease B, serotonin and GABA pathways, and immune activation via lipopolysaccharide (LPS). Emerging microbiota-targeted therapeutic strategies, including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), are critically evaluated in light of current evidence from BED and related eating disorders. Despite the promising mechanistic rationale, rigorous clinical trials remain scarce. This review highlights several priorities for future research, and the development of precision medicine strategies integrating established therapeutic approaches with emerging microbiota-targeted interventions.},
}

@article {pmid42948751,
year = {2026},
author = {Yang, Z and Lv, Q and Xu, Q and Chen, Y and Yang, Y and Li, Z and Che, H and Wang, G and Wei, W and Wu, J and Han, J},
title = {Reprogramming gut microbiota and targeting CXCL1: The multifaceted mechanism of PLP1 in ameliorating alcohol-induced liver disease.},
journal = {Acta pharmaceutica Sinica. B},
volume = {16},
number = {10},
pages = {6686-6704},
pmid = {42948751},
issn = {2211-3835},
abstract = {Hepatic inflammation and gut barrier dysfunction are core pathologies of alcohol-associated liver disease (ALD), yet effective therapies remain limited. Pueraria lobata polysaccharide (PLP1), a key active constituent of P. lobata Radix, has demonstrated hepatoprotective potential; however, its underlying mechanisms remain poorly understood. In this study, we sought to elucidate the therapeutic mechanism of PLP1 against experimental ALD by integrating proteomics, metabolomics, and gut microbiota analyses. We demonstrated that PLP1 initially functions through a microbiota-dependent pathway, transferable by fecal microbiota transplantation (FMT), to restore gut barrier integrity and suppress the gut‒LPS‒TLR4 inflammatory axis. Furthermore, PLP1 exerted a direct, microbiota-independent effect, maintaining its therapeutic efficacy in antibiotic-depleted mice. Mechanistically, PLP1 directly and specifically targets CXCL1, promoting its ubiquitin-mediated proteasomal degradation as confirmed by biophysical assays. The functional necessity of this interaction was definitively established via comprehensive genetic manipulation of CXCL1 in vitro and in vivo. Specifically, CXCL1 overexpression reversed PLP1's benefits, whereas CXCL1 knockdown mimicked its effects and occluded any additional benefit from PLP1. Overall, PLP1 ameliorates ALD by independently targeting both extrinsic and intrinsic inflammatory triggers. This study reveals the multifaceted pharmacology of a natural polysaccharide and validates a dual-pronged therapeutic strategy for ALD.},
}

@article {pmid42949032,
year = {2026},
author = {Axelrad, JE and Allegretti, JR},
title = {Preventing Clostridioides difficile Infection and Recurrence: Practical Strategies for Clinical Practice.},
journal = {The American journal of gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000004239},
pmid = {42949032},
issn = {1572-0241},
abstract = {Clostridioides difficile infection (CDI) is a major cause of morbidity, mortality, and healthcare utilization worldwide. Although advances in antimicrobial stewardship and infection prevention have reduced healthcare-associated disease in some settings, the incidence of community-associated CDI and the persistent burden of recurrent CDI (rCDI) continue to pose substantial clinical challenges. Because recurrent disease is fundamentally driven by persistent disruption of the intestinal microbiome and loss of colonization resistance, prevention has emerged as the central strategy for reducing long-term disease burden. This review summarizes contemporary evidence supporting prevention of both incident and rCDI, emphasizing practical approaches for gastroenterologists. Primary prevention centers on minimizing modifiable risk factors through antimicrobial stewardship, infection prevention and control, diagnostic stewardship to distinguish colonization from infection, and strategies to preserve the intestinal microbiome. For patients with CDI, we review evidence supporting extended antibiotic regimens, oral vancomycin prophylaxis during subsequent systemic antibiotic exposure, and microbiome restoration therapies, including conventional fecal microbiota transplantation and US Food and Drug Administration-approved microbiota-based therapies, which have transformed secondary prevention by restoring microbial diversity and colonization resistance. Special consideration is given to populations at particularly high risk for recurrence, including older adults, immunocompromised individuals, transplant recipients, and patients with inflammatory bowel disease. Finally, we discuss emerging preventive strategies, including precision risk stratification, microbiome- and metabolome-based biomarkers, bile acid modulation, and approaches targeting asymptomatic colonization. Together, these advances signal a paradigm shift from treating CDI episodes to implementing personalized preventive strategies that interrupt the cycle of recurrent disease and improve long-term patient outcomes.},
}

@article {pmid42950665,
year = {2026},
author = {Zhang, Y and Cheng, Y and Li, F and Song, J and Zou, W and Kuang, H},
title = {Gut microbiota-derived 1H-Indole-3-propanoic acid deficiency mediates BPB-induced decidualization impairment via TLR4/NF-κB pathway.},
journal = {Journal of hazardous materials},
volume = {518},
number = {},
pages = {143979},
doi = {10.1016/j.jhazmat.2026.143979},
pmid = {42950665},
issn = {1873-3336},
abstract = {As an important alternative to bisphenol A (BPA), the reproductive toxicity of bisphenol B (BPB) has drawn increasing concern, but the mechanism by which BPB impairs uterine decidualization remains unclear. This study investigated whether early pregnancy BPB exposure impairs decidualization via the "gut microbiota-1H-Indole-3-propanoic acid (IPA)-Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB)" axis. Results showed that BPB inhibited embryo implantation, decidual cell proliferation, angiogenesis, and disrupted intestinal barrier integrity. 16S rRNA sequencing and metabolomics revealed that BPB induced gut dysbiosis (reduction in Lactobacillus) and decreased serum IPA, with IPA positively correlated with Lactobacillus abundance. Network pharmacology predicted that IPA targets were enriched in the TLR4/NF-κB pathway. Fecal microbiota transplantation confirmed that transferring BPB-exposed microbiota replicated decidualization impairment and IPA reduction. Exogenous IPA supplementation inhibited BPB-induced TLR4/NF-κB activation and inflammatory cytokine release, and rescued decidualization. The TLR4 inhibitor TAK-242 partially restored decidualization function. In summary, early pregnancy BPB exposure reduces IPA-producing bacteria such as Lactobacillus, leading to decreased IPA, which subsequently activates the uterine TLR4/NF-κB pathway and impairs decidualization. Supplementation of IPA or TLR4 inhibition effectively rescues this impairment, providing a potential target for intervention in environmentally related reproductive disorders.},
}

@article {pmid42932178,
year = {2026},
author = {Wang, C and Li, X and Wang, Y and Cheng, J and Guan, R and Yang, G},
title = {Fucoxanthin and the gut microbiota-organ axis: linking low bioavailability, microbial metabolites and multi-organ protection.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6fo04416f},
pmid = {42932178},
issn = {2042-650X},
abstract = {Fucoxanthin is a marine carotenoid whose broad effects in experimental models contrast with its limited oral bioavailability. Human exposure to fucoxanthin-derived compounds varies with the food matrix and dosing regimen, with fucoxanthinol being the principal reported circulating metabolite. This review evaluates the proposed fucoxanthin-gut microbiota-organ framework across the gut-liver, gut-brain, and gut-lung axes, systemic metabolism, and tumor biology and immunity, distinguishing direct fucoxanthin evidence from mechanistic extrapolation and assessing dietary dose relevance. Animal studies associate fucoxanthin with microbiota remodeling, improved intestinal barrier function, and reduced lipopolysaccharide translocation. These alterations could influence short-chain fatty acid, bile acid, and tryptophan-derived metabolite signaling, although complete microbiota-metabolite-receptor pathways remain insufficiently validated. Fecal microbiota transplantation supports a microbial contribution to colorectal cancer protection in one mouse model, whereas gut-brain and gut-lung mechanisms remain largely inferential. Many nominal human-equivalent doses derived from animal studies exceed estimated dietary intakes, and cellular fucoxanthin concentrations often exceed circulating human fucoxanthinol concentrations. Human colonic exposure remains unquantified and cannot be inferred from plasma concentrations. Future studies should integrate causal models, luminal and systemic exposure measurements, targeted metabolomics, and human trials to establish the nutritional relevance of fucoxanthin.},
}

@article {pmid42932232,
year = {2026},
author = {Gridhati, S and Dasari, SS and Shanmughanathan, S and Koushik, AK and Sridharan, KS and Kanuri, SD and Medagam, RR},
title = {Clinical Profile and Outcomes of Clostridioides Difficile Infection in Noninflammatory Bowel Disease Patients: A Retrospective Study from a Tertiary Care Center.},
journal = {Annals of African medicine},
volume = {},
number = {},
pages = {},
doi = {10.4103/aam.aam_841_26},
pmid = {42932232},
issn = {0975-5764},
abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is one of the leading causes of healthcare-associated and antibiotic-associated diarrhea and is associated with significant morbidity and mortality. Data regarding the clinical characteristics and outcomes of CDI among noninflammatory bowel disease (non-IBD) patients remain limited. This study aimed to evaluate the clinical profile, outcomes, and predictors of prolonged hospitalization among patients with CDI.

MATERIALS AND METHODS: This retrospective study included 69 adult patients diagnosed with CDI between November 2024 and November 2025. Patients with inflammatory bowel disease, previous fecal microbiota transplantation, or incomplete records were excluded. Demographic, clinical, laboratory, and microbiological data were analyzed. Univariate and multivariate regression analyses were performed to identify the factors associated with prolonged hospital stay.

RESULTS: The mean age of the study population was 71.0 ± 16.4 years and males constituted 56.5% of patients. Hospital-acquired infection accounted for 89.9% of cases, whereas 10.1% were community-acquired. Diabetes mellitus was present in 76.6% of patients. Piperacillin-tazobactam and cephalosporins were the most frequently used antibiotics before diagnosis. The median duration of hospitalization was 15.4 days (interquartile range: 10-19 days). Mortality occurred in 2.9% of patients. Increasing age, diabetes mellitus, and prolonged antibiotic exposure before diagnosis were independently associated with prolonged hospital stay.

CONCLUSION: Elderly patients with diabetes mellitus represented the majority of noninflammatory bowel disease patients with CDI. Hospital-acquired infection predominated, advanced age, diabetes mellitus, and prolonged antecedent antibiotic exposure were associated with prolonged hospitalization.},
}

@article {pmid42934727,
year = {2026},
author = {Liu, Y and Wu, X and Guo, Y and Mei, W and Gao, R and Wang, F and Chen, C and Wang, L and Hao, Y and Wu, T and Yao, X},
title = {Multi-omics analysis reveals that sleep deprivation exacerbates intestinal barrier injury via the microbiota-dependent taurodeoxycholic acid/group 3 innate lymphoid/IL-22 axis.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {},
pmid = {42934727},
issn = {1479-5876},
support = {82403215//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Sleep Deprivation/microbiology/immunology/pathology ; Interleukin-22 ; *Interleukins/metabolism ; *Multiomics ; *Intestinal Barrier Function ; *Lymphocytes/metabolism ; *Immunity, Innate ; Mice, Inbred C57BL ; Male ; *Intestines/pathology ; Fecal Microbiota Transplantation ; Mice ; *Gastrointestinal Microbiome ; *Microbiota ; },
abstract = {BACKGROUND: Clinical studies demonstrated a correlation between sleep dysfunction and intestinal diseases. However, the detailed interactions and underlying mechanisms linking sleep disruption to intestinal microenvironment remain poorly understood.

METHODS: We employed the Curling Prevention by Water (CPW) paradigm to establish a mouse model of sleep deprivation (SD) for durations ranging from 0 to 96 h. The dynamic changes in the intestinal microenvironment were systematically profiled using multi-omics approaches, including metagenomic sequencing, untargeted metabolomics and RNA sequencing. The causal role of microbial dysbiosis and the underlying mechanisms were further investigated using germ-free mice, fecal microbiota transplantation (FMT), flow cytometry, and targeted intervention.

RESULTS: The intestinal microenvironment was highly sensitive to SD. Distinct microbial communities and metabolite profiles were observed among brief SD (< 24 h of SD), prolonged SD (24-96 h of SD) and control. Brief SD triggered a self-regulatory response of the gut microbiota, characterized by an increase in certain beneficial bacteria (e.g., Parabacteroides goldsteinii). In contrast, prolonged SD shaped a pro-inflammatory microbial structure, characterized by reduced Akkermansia muciniphila and enriched Pseudomonadota. Multi-omics analysis revealed that SD significantly inhibited microbial bile acid metabolism, particularly taurodeoxycholic acid (TDCA), and impaired intestinal barrier function while suppressing the intestinal immune response to bacteria antigens. Mechanistically, SD exacerbated intestinal barrier damage by inhibiting the TDCA/group 3 innate lymphoid cells (ILC3)/IL-22 axis. Supplementation with TDCA effectively restored ILC3 function, IL-22 production, and barrier integrity in SD mice. Furthermore, FMT from patients with sleep dysfunction significantly disturbed intestinal microenvironment and increased serum cortisol by regulating gut microbiota and inhibiting TDCA/ILC3/IL-22 axis.

CONCLUSION: This study dynamically delineates how SD disrupts intestinal homeostasis by reshaping the gut microbiota and suppressing the TDCA/ILC3/IL-22 axis. These findings provide novel mechanistic insights and identify potential therapeutic targets for sleep dysfunction-associated intestinal complications.},
}

Animals
*Sleep Deprivation/microbiology/immunology/pathology
Interleukin-22
*Interleukins/metabolism
*Multiomics
*Intestinal Barrier Function
*Lymphocytes/metabolism
*Immunity, Innate
Mice, Inbred C57BL
Male
*Intestines/pathology
Fecal Microbiota Transplantation
Mice
*Gastrointestinal Microbiome
*Microbiota

@article {pmid42935761,
year = {2026},
author = {Whitman, BT and Karimianghadim, R and Auch, B and Liachko, I and , and Monaghan, TM and Pakpour, S and Kao, D},
title = {Metabolic network restoration, not donor microbial engraftment, associates with resolution of recurrent Clostridioides difficile infection.},
journal = {iScience},
volume = {29},
number = {11},
pages = {117907},
pmid = {42935761},
issn = {2589-0042},
abstract = {Fecal microbiota transplantation (FMT) effectively prevents recurrent Clostridioides difficile infection (rCDI). However, the mechanisms underpinning FMT efficacy are incompletely understood. We used proximity-ligation metagenomics, metaproteomics, and metabolomics to profile dynamic changes in rCDI. We analyzed samples collected from the first 7 responders during a clinical trial comparing two donor-based treatments (lyophilized FMT [LFMT] or lyophilized sterile fecal filtrate [LSFF], free of intact microorganisms) to prevent rCDI. LSFF is enriched in Caudoviricetes, lipids, fatty acids, and human and extracellular bacterial proteins compared with LFMT. LFMT recipients had donor microbial engraftment, while LSFF recipients achieved only partial microbial community recovery without donor's contribution. Our multi-omics analyses identified a functional convergence following both treatments, shifting away from oxidative and antibiotic stress survival pathways toward enhanced carbon-nitrogen utilization pathways, suggesting that FMT mechanisms may involve metabolic reprogramming and host-microbial amino acid co-metabolism. Our findings provide important hypothesis-generating insights that warrant further validation.},
}

@article {pmid42935951,
year = {2026},
author = {Shi, X and Wang, S and Ouyang, W},
title = {Microbial-derived metabolites in cancer: evidence boundaries, immune mechanisms and translational pathways.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1947330},
pmid = {42935951},
issn = {1664-3224},
mesh = {Humans ; *Neoplasms/immunology/metabolism/microbiology/therapy ; Animals ; *Bacteria/metabolism ; Translational Research, Biomedical ; Antineoplastic Agents/therapeutic use ; *Gastrointestinal Microbiome ; },
abstract = {Microbial metabolites can suppress or promote tumor development and modify treatment response, but the direction of an effect depends on its chemical identity, anatomical source, concentration and host target. This narrative review critically examines short-chain fatty acids, tryptophan derivatives, secondary bile acids, colibactin, cyclic dinucleotides and microbial activities that alter anticancer drugs. We distinguish individual metabolites from postbiotic preparations, microbial components and enzymes, and separate microbial production from host-microbial co-metabolism. Mechanistic examples include butyrate-dependent chromatin regulation, macrophage aryl hydrocarbon receptor signaling, microbial agonists of STING, colibactin-induced DNA cross-links and bacterial conversion of gemcitabine or irinotecan metabolites. For each, we consider the experimental model, evidence for causality, physiological exposure and limits of human translation. Particular attention is given to apparently conflicting short-chain-fatty-acid findings across checkpoint inhibitors, the conditional effects of dietary fiber, and discordance between experimental drug inactivation and human pancreatic tumor profiling. Human studies support selected biomarker associations and early intervention feasibility, including fecal microbiota transplantation and engineered bacterial delivery, but do not establish a general metabolite-based treatment strategy. We therefore propose a seven-step research framework linking patient sampling, direct quantification and source attribution, causal and functional testing, external biomarker validation, intervention selection, pharmacodynamic monitoring and prospectively defined clinical endpoints. Its contribution is to make the evidence required for each translational decision explicit while distinguishing clinically useful prediction from a causally justified intervention.},
}

Humans
*Neoplasms/immunology/metabolism/microbiology/therapy
Animals
*Bacteria/metabolism
Translational Research, Biomedical
Antineoplastic Agents/therapeutic use
*Gastrointestinal Microbiome

@article {pmid42937775,
year = {2026},
author = {He, Y and Lin, F and Huang, H and Chen, Q},
title = {Mapping and visualizing global research trends in gut microbiota and autism spectrum disorder: A bibliometric analysis (2015-2024).},
journal = {Medicine},
volume = {105},
number = {43},
pages = {e51247},
pmid = {42937775},
issn = {1536-5964},
support = {2024Y9016//the Joint Funds for the Innovation of Science and Technology of Fujian Province/ ; },
mesh = {Humans ; *Bibliometrics ; *Autism Spectrum Disorder/microbiology ; *Gastrointestinal Microbiome/physiology ; *Biomedical Research/trends ; },
abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder with increasing research interest in its association with the gut microbiota. However, the knowledge structure and development of this field have not been systematically analyzed.

METHODS: We conducted a comprehensive bibliometric analysis of English-language publications related to ASD and gut microbiota from 2015 to 2024 using the Web of Science Core Collection. We used the bibliometrix package in R, VOSviewer, and CiteSpace for analysis, focusing on publication trends, geographic and institutional contributions, prominent authors and journals, citation patterns, keyword dynamics, and thematic clusters.

RESULTS: A total of 1309 publications were included, involving corresponding authors from 64 countries or regions. The annual number of publications steadily increased from 2015 to 2022, followed by a slight decline in 2023 and a partial rebound in 2024, with the US and China contributing the most. Leading authors and teams were primarily based in North America and Europe. Thematic evolution revealed a shift from early mechanistic research to intervention-focused topics, such as short-chain fatty acids, fecal microbiota transplantation, and probiotics.

CONCLUSION: Research on ASD and gut microbiota is progressing from theoretical exploration toward early-stage translational research, with increasing investigation of potential clinical applications. Future studies should emphasize multi-omics integration, mechanistic validation, and international collaboration. This bibliometric analysis offers a comprehensive overview to inform and guide future research in this rapidly evolving field.},
}

Humans
*Bibliometrics
*Autism Spectrum Disorder/microbiology
*Gastrointestinal Microbiome/physiology
*Biomedical Research/trends

@article {pmid42938706,
year = {2026},
author = {Iaquinto, G and Picariello, E and Iaquinto, S and Melina, R and Sellitto, C and Sellitto, S and Cataldo, G and Pastore, R and Rotondi Aufiero, V},
title = {Novel Therapeutic Strategies for Active Crohn's Disease: Targeting Pathobionts and Host-Microbe Interactions.},
journal = {Antibiotics (Basel, Switzerland)},
volume = {15},
number = {10},
pages = {},
pmid = {42938706},
issn = {2079-6382},
abstract = {Crohn's disease (CD) is a chronic inflammatory disorder characterized by complex interactions among genetic susceptibility, environmental factors, dysregulated immune responses, and alterations of the intestinal microbiota. Although corticosteroids, immunomodulators, biologics, and advanced small-molecule therapies remain central to disease management, a substantial proportion of patients experience primary non-response, loss of response, or treatment-related adverse effects. This has stimulated interest in complementary therapeutic strategies targeting host-microbe interactions and intestinal microbial homeostasis. This review critically examines emerging microbiome-directed approaches for CD, with particular emphasis on pathobionts such as adherent-invasive Escherichia coli (AIEC). We discuss the available evidence for antibiotics, antimicrobial peptides (AMP), gut bacteriophages, fecal microbiota transplantation (FMT), and selected nutraceutical and dietary interventions. While some approaches show promising biological or clinical signals, the strength of evidence varies considerably, ranging from in vitro and animal studies to randomized clinical trials and meta-analyses. Antibiotic therapies targeting intestinal pathogens have shown heterogeneous results, suggesting the need for pathogen-guided and intracellularly active antimicrobial strategies. Novel approaches, including AIEC-specific phages and AMP-based interventions, represent promising microbiome-sparing alternatives capable of selectively modulating disease-associated microorganisms. Furthermore, FMT and nutraceuticals may contribute to restoring microbial balance and strengthening intestinal homeostasis, although their efficacy requires further validation in controlled clinical trials. Overall, these strategies support a transition toward precision medicine approaches integrating microbial profiling, host immune characterization, and targeted antimicrobial interventions to improve therapeutic outcomes in CD.},
}

@article {pmid42938745,
year = {2026},
author = {Berry, P and Bharadiya, V and Khanna, S},
title = {Barriers to Diagnosis and Treatment of Clostridioides difficile Infection: A Narrative Review.},
journal = {Antibiotics (Basel, Switzerland)},
volume = {15},
number = {10},
pages = {},
pmid = {42938745},
issn = {2079-6382},
abstract = {Clostridioides difficile infection (CDI) remains a major cause of healthcare-associated diarrhea and is being increasingly recognized in community settings. The management of CDI is complicated by diagnostic uncertainty, recurrent disease, and uneven access to newer therapies. Clinicians must distinguish infection from colonization, individualize therapy selection, and anticipate barriers to recurrence prevention. This narrative review examines diagnostic and therapeutic barriers in adult CDI care, with particular emphasis on the U.S. healthcare, regulatory, and reimbursement setting. Several guidelines prefer fidaxomicin for an initial nonfulminant CDI episode when available. Oral vancomycin is an effective alternative, and metronidazole is reserved for initial nonsevere CDI when preferred agents are unavailable. Antibiotic options for recurrent CDI include standard or extended-pulsed fidaxomicin and standard-course or tapered-and-pulsed vancomycin regimens. After antibacterial treatment, conventional fecal microbiota transplantation (FMT) and two FDA-approved microbiota products, fecal microbiota spores, live-brpk (VOS) and fecal microbiota, live-jslm (RBL), may be used in appropriately selected patients to prevent another recurrence. In ECOSPOR III, recurrence through 8 weeks was 12.4% of VOS recipients and 39.8% of placebo recipients. In PUNCH CD3, Bayesian model-estimated treatment success through 8 weeks was 70.6% with RBL and 57.5% with placebo. Because the trials used different populations, endpoints, definitions, and analytical frameworks, these figures should not be interpreted as a head-to-head comparison. The discontinuation of bezlotoxumab in the United States and reduced availability of stool bank-derived FMT have further constrained recurrence prevention options. Practical considerations include diagnostic stewardship, assessment of recurrence risk, and timely access to indicated recurrence prevention therapy.},
}

@article {pmid42939113,
year = {2026},
author = {Zhang, X and Ma, Y and Liu, H and Yang, Y and Wu, Z},
title = {Pediococcus acidilactici Long21 Alleviates Intestinal Sensitivity and Improves Gut Health in German Shepherd Dogs by Regulating Intestinal Metabolic Profiles.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {20},
pages = {},
pmid = {42939113},
issn = {2076-2615},
support = {(No.32172749)//National Natural Science Foundation of China/ ; Nos.2022YFF1100102, 2022YFC2105005//National Natural Science Foundation of China/ ; },
abstract = {Background: Canine intestinal sensitivity is a multifactorial functional gastrointestinal disorder characterized by recurrent soft feces, impaired nutrient utilization, and low-grade intestinal inflammation, and it acts as a major trigger for chronic gastrointestinal discomfort in dogs. Conventional antibiotic therapy causes side effects and drug resistance. Probiotics modulate host physiology, immunity, and metabolism, serving as promising alternatives for improving canine intestinal health. This study aimed to compare the gut microbiota of healthy and sensitive German shepherd dogs, screen and identify candidate probiotics, and verify their efficacy in ameliorating canine intestinal dysfunction and hypersensitivity. Results: Fecal microbiota transplantation from healthy dogs effectively improved these fecal indicators and was associated with enhanced serum antioxidant and anti-inflammatory capacities in intestinal-sensitive dogs (p < 0.05). Additionally, 16S rRNA sequencing revealed that healthy German Shepherd dogs had higher intestinal microbial α- and β-diversity, with Pediococcus acidilactici enriched in healthy dogs and Shigella increased in diarrheic dogs (p < 0.05). P. acidilactici Long21 intervention, either alone or combined with its fermentation supernatant, significantly improved fecal traits; reduced pathogenic bacterial abundance; increased the apparent digestibility of dry matter, crude fibre, and ether extract; and was associated with normalized antioxidant function and inflammatory indicators in German Shepherd dogs with intestinal sensitivity (p < 0.05). We identified 2085 differentially abundant metabolites enriched in amino-acid and energy metabolism using untargeted metabolomics, with glutamate, malate, and pyruvate as hub metabolites correlated with nutrient digestibility and fecal traits. Conclusions: Intestinal flora imbalance is associated with intestinal sensitivity-related diarrhea in dogs. P. acidilactici Long21 supplementation alleviated intestinal sensitivity-associated diarrhea and improved intestinal health, possibly through coordinated changes in gut microbiota, metabolic profiles, and nutrient utilization. These findings provide a theoretical basis and a candidate strain for microecological intervention, although causal mechanisms remain to be confirmed.},
}

@article {pmid42939185,
year = {2026},
author = {Fu, L and Xue, Y and Wang, Y and Zhao, S and Wang, Q and Che, H},
title = {Potential Feasibility and Perspectives of Fecal Microbiota Transplantation for Restoring Gut Function in Giant Pandas.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {20},
pages = {},
pmid = {42939185},
issn = {2076-2615},
support = {//China Agricultural University-Sichuan Advanced Agricultural & Industrial Institute/ ; },
abstract = {Although the giant panda (Ailuropoda melanoleuca) relies almost exclusively on bamboo, its carnivore-like gastrointestinal tract has limited capacity for fiber digestion. The gut microbiota contributes to bamboo-derived nutrient utilization, although the extent of this contribution remains limited. Captivity-associated dietary and environmental changes frequently disrupt this microbial ecosystem, resulting in impaired digestive function and reduced physiological resilience. Conventional interventions, including antibiotics and single-strain probiotics, are generally insufficient to restore the complexity and stability of the gut microbiota. Fecal microbiota transplantation (FMT), which reconstructs the gut microbial ecosystem by transferring an intact microbial community, has demonstrated therapeutic potential in humans and various animal models. However, its feasibility in giant pandas remains unclear because their short intestinal tract, absence of fermentation chambers, rapid gastrointestinal transit, and host-mediated ecological filtering substantially limit donor microbiota engraftment. This review evaluates the biological rationale and technical feasibility of oral FMT in giant pandas by integrating evidence from gastrointestinal physiology, microbial ecology, and conservation medicine. This review identifies the principal barriers to microbial engraftment. It synthesizes a giant panda-specific framework from the available literature, encompassing function-oriented donor selection, optimized microbial delivery strategies, and multidimensional efficacy assessment. Collectively, this synthesis provides a theoretical foundation for future FMT research in giant pandas and offers a conceptual reference for microbiota-based interventions in the conservation of endangered wildlife.},
}

@article {pmid42939950,
year = {2026},
author = {Vijverman, L and Maddalena, T and Delrue, C and Speeckaert, MM},
title = {The Gut-Kidney Axis in Chronic Kidney Disease: Microbial Dysbiosis, Host-Microbial Metabolism, and Emerging Therapeutic Strategies.},
journal = {Biomedicines},
volume = {14},
number = {10},
pages = {},
pmid = {42939950},
issn = {2227-9059},
abstract = {Chronic kidney disease (CKD) appears linked to changes in the gut microbiota, intestinal barrier defects, and microbiota-driven changes in metabolite profiles. Experimental evidence links gut microbiota disturbances to kidney injury through pathways such as microbial metabolism, inflammation, immune signals, and epithelial barrier dysfunction. Still, applying this knowledge in clinical practice for patients with CKD remains difficult. For instance, one study on indoxyl sulfate and p-cresyl sulfate levels in a patient showed that, beyond being synthesized by the intestinal microbiota, the host can also metabolize or alter these metabolites. In addition, they undergo impaired renal clearance and can be secreted by the tubules. Moreover, most human microbiome-related studies are observational, making it difficult to determine the causal role of bacterial dysbiosis. Disease, dietary factors, medication, and other comorbid conditions are major confounders. Microbiota-directed means of altering the composition of the microbiota, such as changing diet, using prebiotics, probiotics, synbiotics, oral adsorbents, and even fecal microbiota transplantation, have, to varying degrees, affected the composition of the gut microbiota, levels of uremic toxins, short-chain fatty acids, and markers of inflammation. They have also been connected to leaky gut syndrome. However, evidence that these actions delay eGFR decline or prevent kidney failure, cardiovascular events, hospitalization, or mortality remains limited. Postbiotics and microbiota-derived metabolites in pure form are distinct experimental therapies and need to be assessed independently. This article reviews the gut kidney axis at different levels of evidence and distinguishes preclinical mechanisms, human associations, surrogate biomarker responses, and clinical outcomes. It points out why impressive mechanistic and biomarker results have not translated into better kidney or cardiovascular outcomes. Future research should use standardized methodologies, provide more detail on microbial functions and host metabolite metabolism, and test microbiome-targeted therapies in sufficiently powered randomized controlled trials with meaningful endpoints.},
}

@article {pmid42940167,
year = {2026},
author = {Yu, L and He, L and Lu, Y},
title = {Gut Microbiota-Driven Neuroimmune Crosstalk in Ulcerative Colitis: From Mechanisms to Therapeutic Implications.},
journal = {Biomedicines},
volume = {14},
number = {10},
pages = {},
pmid = {42940167},
issn = {2227-9059},
abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease in which epithelial barrier injury, microbial perturbation, dysregulated mucosal immunity, and altered neural signaling converge. Although dysbiosis is frequently reported in UC, taxonomic shifts alone do not explain how microbial signals are translated into mucosal inflammation, urgency, pain, relapse, or heterogeneous therapeutic responses. This review develops a focused framework of gut microbiota -driven neuroimmune crosstalk, defined as bidirectional communication through which microbial communities and their metabolites regulate epithelial, neuronal, glial, enteroendocrine, and immune compartments, while neural and immune signals reshape barrier function and microbial ecology. We synthesize evidence on short-chain fatty acids, tryptophan-derived indoles, serotonin signaling, bile acids, microbe-associated molecular patterns, vagal anti-inflammatory reflexes, enteric neurons, sensory neurons, enteric glia, macrophages, dendritic cells, T cells, innate lymphoid cells, mast cells, and neutrophils. Therapeutic opportunities include diet, prebiotics, probiotics, postbiotics, fecal microbiota transplantation, metabolite-based interventions, vagus nerve stimulation, neuropeptide or serotonin pathway modulation, and combination strategies with established anti-inflammatory therapies. UC-specific evidence is emphasized where available, with explicit distinction between human UC findings, broader inflammatory bowel disease (IBD) evidence, experimental colitis models, and general mechanistic studies. A microbiota-neuroimmune framework may help move UC research beyond descriptive dysbiosis toward mechanism-guided precision therapy; however, most causal neuroimmune pathways still require validation in well-phenotyped human UC cohorts, and the proposed endotypes in this review are hypothesis-generating and require prospective validation.},
}

@article {pmid42940367,
year = {2026},
author = {Liu, J and Wang, Q and Bian, X and Han, Y and Liang, J and Zhang, R and Xiao, Y and Chen, Q and Zhang, X and Sun, X},
title = {Euscaphic Acid from Rosa roxburghii Tratt Fruit Ameliorates Ulcerative Colitis by Modulating Oxidative Stress, Inflammation, Gut Microbiota, and Metabolism.},
journal = {Foods (Basel, Switzerland)},
volume = {15},
number = {20},
pages = {},
pmid = {42940367},
issn = {2304-8158},
support = {20240602089RC//Jilin Province Science and Technology Department/ ; },
abstract = {Although euscaphic acid (EA)-the main active component of Rosa roxburghii Tratt fruit-possesses potential antioxidant, anti-inflammatory, and intestinal protective effects, the mechanisms underlying these properties remain unclear. This study aimed to investigate whether EA can alleviate dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) through multiple mechanisms such as inhibiting oxidative stress, regulating inflammation, remodeling the gut microbiota, and restoring metabolic disturbances. Using a DSS-induced mouse model of UC and integrating histopathological examination, Western blotting, 16S rRNA sequencing, untargeted metabolomics, transcriptome sequencing, and fecal microbiota transplantation, EA's mechanisms of action were investigated at multiple levels, including the tissue, microbial, and metabolic levels. EA counteracted DSS-induced alterations in MPO, SOD, MDA, IL-6, IL-1β, and TNF-α. In addition, EA intervention improved UC and reversed the reduction in Bacteroides uniformis (B. uniformis) in UC mice. Further studies confirmed that B. uniformis is a key species mediating the UC-alleviating effects of EA. Metabolomics analysis indicated that EA could mitigate the effects of metabolic disorders; transcriptomic analysis indicated that it inhibits inflammatory signaling pathways; and multi-omics analysis further revealed that it alleviates UC by restoring the gut microbiota and correcting metabolic disorders while simultaneously inhibiting oxidative and pro-inflammatory pathways.},
}

@article {pmid42943387,
year = {2026},
author = {Biazzo, M and Soriani, M and Micallef, MP and Zaky, E and Podrini, C},
title = {Precision Microbiome Interventions in Oncology: From Predictive Biomarkers to Therapeutic Modulation of Immunotherapy Outcomes.},
journal = {Microorganisms},
volume = {14},
number = {10},
pages = {},
pmid = {42943387},
issn = {2076-2607},
support = {Cancer Research Programme 2024, CRP-2024-12//Cancer Research Innovation Hub Malta Foundation (CRIHM)/ ; },
abstract = {Immune checkpoint inhibitors (ICIs) have transformed the treatment of multiple malignancies, yet durable clinical responses remain limited to a subset of patients. Accumulating evidence identifies the gut microbiome as a regulator of antitumour immunity that can influence treatment efficacy and toxicity through microbial metabolism, epithelial barrier integrity, inflammatory signalling, and host immune responses. This review critically evaluates the microbiome as both a predictive biomarker and therapeutic target in precision oncology. It moves beyond descriptive taxonomic associations by assessing emerging functional and mechanistic models that integrate microbial metabolites, ecological interactions, strain-level variation, and host-microbiome communication. Clinical and translational evidence from melanoma, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, and urothelial carcinoma reveals marked differences in the reproducibility and clinical maturity of reported microbial signatures. Emerging microbiome-targeted strategies, including dietary modulation, faecal microbiota transplantation (FMT), live biotherapeutic products (LBPs), and defined microbial consortia, may enhance ICI responsiveness, with responder-derived FMT providing important early clinical proof of concept. However, inter-individual variability, donor-recipient compatibility, microbial engraftment, the lack of standardised analytical approaches, and unresolved safety and regulatory requirements continue to limit clinical translation. Pending prospective validation, reasonable clinical practice is to avoid unnecessary microbiome-disrupting antibiotics, systematically document diet and concomitant medications, evaluate FMT and LBPs within regulated clinical trials, and interpret microbiome profiles alongside established tumour and host biomarkers rather than as stand-alone tests. Current evidence therefore supports a cautious shift towards functional microbiome-guided precision oncology, providing a foundation for personalised strategies to improve cancer immunotherapy outcomes.},
}

@article {pmid42943475,
year = {2026},
author = {Fusco, W and Margarita, E and Capuano, E and Severino, A and Porcari, S and Varca, S and Galasso, T and Lener, E and Gasbarrini, A and Ianiro, G},
title = {Proteobacteria: A Toolbox for Clinicians.},
journal = {Microorganisms},
volume = {14},
number = {10},
pages = {},
pmid = {42943475},
issn = {2076-2607},
support = {project 32405//My First AIRC Grant 2025 of the AIRC/ ; PNRR-POC-2023-12377319//PNRR 2023/ ; 30203//the Next Gen Clinician Scientist 2024 of the AIRC/ ; FIS00001711//Fondo Italiano per la Scienza of the Italian Ministry of Research/ ; ERC-StG MicroRestore-101221279/ERC_/European Research Council/International ; DONATE ERP-2022-23682517//Joint Programming Initiative on Antimicrobial Re-sistance/ ; },
abstract = {Proteobacteria are a phylum of Gram-negative bacteria that, although normally a minor component of the healthy gut microbiota, can be markedly increased in many conditions. Their overgrowth is in fact linked to inflammation, impaired epithelial barrier function, and diseases such as inflammatory bowel disease, metabolic syndrome, and gastrointestinal cancers. Key species, like Escherichia coli and Helicobacter pylori, can promote disease through specific etiopathogenetic mechanisms, from genotoxin production to immune activation: this peculiarity can be used for diagnostic purposes, and in some cases even as therapeutics. Emerging microbiota-targeted therapies-such as dietary modulation, probiotics, fecal microbiota transplantation, bacteriophages, and engineered bacteria-aim to restore microbial balance. This narrative review deals with the dual role of Proteobacteria as both pathogens and diagnostic-therapeutic tools, which is crucial for advancing personalized microbiome-based medicine.},
}

@article {pmid42943521,
year = {2026},
author = {Zheng, M and Chen, R and Wei, Y and Zeng, Y and Wang, D and Ren, Y and Wang, X and Liu, L and Yang, X and Shi, L and Xin, L and Yang, J},
title = {Ganoderma lucidum Sporoderm-Broken Spore Powder (GLSP) Remodels the Gut Microbiota and Promotes Tryptophan-Derived Indole Metabolites to Maintain Intestinal Homeostasis.},
journal = {Microorganisms},
volume = {14},
number = {10},
pages = {},
pmid = {42943521},
issn = {2076-2607},
support = {32471206//National Natural Science Foundation of China/ ; 32271201//National Natural Science Foundation of China/ ; 2024YFA1107402//National Key Research and Development Program of China/ ; 24JCZDJC00460//Key Project of Tianjin Natural Science Foundation/ ; },
abstract = {Ganoderma lucidum sporoderm-broken spore powder (GLSP) has been historically documented for its anti-aging and anti-tumor effects. Although several studies have reported that GLSP and related substance may improve physiological function by regulating the gut microbiota, the underlying mechanisms and their effect on intestinal function remains largely unknown. In this study, we comprehensively investigated the impact of dietary GLSP on intestinal epithelial dynamics and barrier function, assessed by single-cell RNA sequencing (scRNA-seq), using murine models spanning physiological homeostasis and DSS-induced intestinal injury. Our study reveals that GLSP protects intestinal epithelia against chemical and age-related barrier injury by promoting the coordinated expansion of stem/progenitor compartments and restoring both the mucus and physical barriers. Gut microbiota involvement was confirmed via antibiotic-treated mice and fecal microbiota transplantation (FMT). FMT from GLSP-diet donors successfully recapitulated the protective effects in gut microbiota-depleted recipient mice. Multi-omics integration of 16S rRNA sequencing and metabolomic profiling identified the enrichment of SCFA-producing genera, and previously unrecognized microbial metabolites, such as indole-2-carboxylic acid, 3-Methyloxindole, and 4-hydroxyindole. These microbial metabolites are likely to play an essential role in reprogramming the intestinal metabolome, particularly tryptophan-indole metabolic pathways, to mediate intestinal homeostasis. These findings provide novel insights and potential directions for the development of new drugs targeting intestinal injury.},
}

@article {pmid42943648,
year = {2026},
author = {He, Y and Zhu, X and Huang, Z and Yang, X and Yi, B},
title = {Ecological Editing: Decoupling Microbial Signals from Metabolic Noise to Reprogram the Gut Ecosystem.},
journal = {Microorganisms},
volume = {14},
number = {10},
pages = {},
pmid = {42943648},
issn = {2076-2607},
support = {82404050//National Natural Science Foundation of China/ ; 82560565//National Natural Science Foundation of China/ ; 20252BAC250152//Key Project of the Natural Science Foundation of Jiangxi Province/ ; 20252BAC250125//Key Project of the Natural Science Foundation of Jiangxi Province/ ; 20252BAC200530//Youth Project of the Natural Science Foundation of Jiangxi Province/ ; GJJ2403619//Scientific and Technological Research Project of the Jiangxi Provincial Department of Education/ ; GJJ2503436//Scientific and Technological Research Project of the Jiangxi Provincial Department of Education/ ; SKJP1320242247//Jiangxi Provincial Health Commission Science and Technology Program/ ; },
abstract = {The translation of microbiome therapeutics is hampered by the stochasticity of faecal microbiota transplantation (FMT), an empirical transfer of undefined biomass confounded by donor heterogeneity, procedural variability, and immunogenic debris. As the field moves towards precision medicine, microbiome engineering is diverging into two philosophies: the subtractive paradigm, which purifies the native ecosystem by removing deleterious metabolites, and the additive paradigm, which assembles functional guilds de novo. In this review, we propose that density-based ecological purification, termed quantitative fractionated microbiota (QFM), may act as an immunological sieve, using washed microbiota transplantation (WMT) as its best-characterised clinical exemplar, to separate therapeutic signals (viable microbiota and bacteriophages) from metabolic noise (for example, pro-inflammatory lipid mediators and glucocorticoid metabolites). We explicitly frame this separation as a conceptual working model rather than an established mechanism: the quantitative assays, cut-off values, and units required to operationalise a signal-to-noise distinction do not yet exist, and we set out what would be needed to develop them. Conversely, live biotherapeutic products (LBPs) offer compositional precision but face a critical bottleneck, namely engraftment failure in colonisation-resistant hosts. We propose that the future lies less in competition between these modalities than in their convergence, which we term the soil-and-seed framework. In this framework, subtractive ecological priming (QFM/WMT) may transiently lower colonisation resistance by liberating niche space and by reducing soluble inflammatory exposure, thereby preparing the mucosa for subsequent engraftment of additive consortia. We describe this hybrid strategy as a hypothesis with an explicit validation roadmap. If it holds, this shift would move microbiome therapy from stochastic biomass transfer towards predictable ecosystem engineering.},
}

@article {pmid42943856,
year = {2026},
author = {Yao, P and Huang, J and Liu, W and Yuan, Q and Lv, J},
title = {Astragalus Polysaccharides Alleviate Inflammatory Damage in Murine Rheumatoid Arthritis by Modulating Th17/Treg Balance via the Gut-Joint Axis.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {20},
pages = {},
pmid = {42943856},
issn = {1420-3049},
support = {CSTB2022NSCQ-MSX0199//Natural Science Foundation of Chongqing/ ; 81903888//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Th17 Cells/drug effects/immunology/metabolism ; *T-Lymphocytes, Regulatory/drug effects/immunology/metabolism ; *Polysaccharides/pharmacology/chemistry ; *Arthritis, Rheumatoid/drug therapy/pathology/immunology/metabolism ; Mice ; *Astragalus Plant/chemistry ; Gastrointestinal Microbiome/drug effects ; Cytokines/metabolism ; *Arthritis, Experimental/drug therapy/pathology/immunology ; *Joints/drug effects/pathology ; Inflammation/drug therapy ; Disease Models, Animal ; Male ; },
abstract = {Astragalus polysaccharides (APSs) have demonstrated protective effects in RA models; however, the underlying microbe-host crosstalk remains unclear. In this study, collagen-induced arthritis (CIA) was established in mice, followed by prophylactic and therapeutic APS administration. The following were then assessed: articular histopathology, splenic Th17/Treg frequencies via flow cytometry, serum and joint cytokine profiles via ELISA and immunohistochemistry, gut microbial metagenomes, and bone erosion via Safranin O-fast green staining. It was found that APS treatment significantly attenuated joint inflammation and bone destruction, rebalanced the Th17/Treg ratio, and reduced pro-inflammatory cytokines (TNF-α and IL-17) while elevating anti-inflammatory IL-10 both systemically and locally. Subsequently, fecal microbiota from APS-treated donor mice was transplanted via oral gavage into CIA recipient mice. APS reversed RA-associated gut dysbiosis by enriching Ligilactobacillus, Lactobacillus, Limosilactobacillus, and Bacteroides, and these microbial shifts closely paralleled diminished articular inflammation and preserved bone architecture. Collectively, these findings indicate that APS mitigates RA progression by reconfiguring the gut microbial ecosystem-favoring beneficial taxa while curbing pathobionts-thereby restoring intestinal homeostasis, normalizing the Th17/Treg axis, and suppressing systemic and articular inflammatory responses.},
}

Animals
*Th17 Cells/drug effects/immunology/metabolism
*T-Lymphocytes, Regulatory/drug effects/immunology/metabolism
*Polysaccharides/pharmacology/chemistry
*Arthritis, Rheumatoid/drug therapy/pathology/immunology/metabolism
Mice
*Astragalus Plant/chemistry
Gastrointestinal Microbiome/drug effects
Cytokines/metabolism
*Arthritis, Experimental/drug therapy/pathology/immunology
*Joints/drug effects/pathology
Inflammation/drug therapy
Disease Models, Animal
Male

@article {pmid42944051,
year = {2026},
author = {Ghidini, M and Sberna, G and Guerrera, LP and Maggi, F and Novazzi, F},
title = {The Gut Virome in Gastrointestinal Cancers: Mechanisms, Biomarkers, and Translational Opportunities.},
journal = {Viruses},
volume = {18},
number = {10},
pages = {},
pmid = {42944051},
issn = {1999-4915},
mesh = {Humans ; *Gastrointestinal Neoplasms/virology/therapy ; *Virome ; *Gastrointestinal Microbiome ; Animals ; Bacteriophages ; Gastrointestinal Tract/virology ; Translational Research, Biomedical ; Biomarkers, Tumor ; Oncogenic Viruses ; Bacteria/virology ; },
abstract = {The gastrointestinal tract contains a dense multi-kingdom ecosystem in which bacteria, fungi, archaea, viruses, the mucosa, and the immune system interact. Although cancer microbiome research has focused mainly on bacteria, the gut virome dominated by bacteriophages may influence gastrointestinal carcinogenesis by reshaping bacterial communities, transferring functional genes, modulating inflammation, and altering treatment response. The strongest evidence comes from colorectal cancer, where multiple cohorts show altered phage diversity, temperate-phage enrichment, disrupted phage-bacteria networks, and reproducible stool-based diagnostic signals. Emerging studies in pancreatic cancer, esophageal adenocarcinoma, hepatocellular carcinoma, and precursor lesions suggest that virome disruption extends beyond colorectal cancer, although evidence remains uneven. Classic oncogenic viruses, including Epstein-Barr virus and hepatitis viruses, provide complementary examples of direct viral carcinogenesis in digestive organs. Anelloviruses are widespread in healthy individuals and are not established causes of cancer, but their abundance and composition may reflect immune status, inflammation, tissue injury, and altered host viral ecology. Virome-related interventions remain clinically immature: fecal microbiota transplantation has reached small phase I/II studies in gastrointestinal cancers, whereas phage, fecal-filtrate, and fecal virome approaches remain preclinical or non-oncology; direct oncolytic viruses have reached late-phase testing. Major barriers include viral dark matter, specimen and assay heterogeneity, disease-related confounding, limited external validation, and weak causal evidence. Standardized, mechanistically anchored, multi-kingdom studies are needed to establish clinical utility.},
}

Humans
*Gastrointestinal Neoplasms/virology/therapy
*Virome
*Gastrointestinal Microbiome
Animals
Bacteriophages
Gastrointestinal Tract/virology
Translational Research, Biomedical
Biomarkers, Tumor
Oncogenic Viruses
Bacteria/virology

@article {pmid42925522,
year = {2026},
author = {Javed, A and Chrysostomou, D and Marchesi, JR and Roberts, L and Hart, AL and Powell, N and Williams, HRT and Hicks, LC and Mullish, BH and Alexander, JL},
title = {Fecal microbiota transplant in the treatment of inflammatory bowel diseases: new perspectives on delivery, mechanism, and clinical positioning.},
journal = {Inflammatory bowel diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/ibd/izag219},
pmid = {42925522},
issn = {1536-4844},
support = {//National Institute of Health Research (NIHR) Imperial Biomedical Research Centre (BRC)/ ; MR/Z504002/1//Medical Research Council (MRC) Clinician Scientist/ ; PG_25008//Bowel Research U.K./ ; },
abstract = {The gut microbiota, a complex and dynamic community of microorganisms, has emerged as a crucial determinant of human health and well-being in recent years. This microbial ecosystem plays a pivotal role in various physiological processes, including nutrient metabolism, immune system regulation, and intestinal homeostasis. Disruptions in the composition and function of the gut microbiota have been implicated in a wide range of diseases, such as Clostridioides difficile infection (CDI) and inflammatory bowel diseases (IBD). The elucidation of the fundamental relationship between human disease and the gut microbiome has positioned fecal microbiota transplantation (FMT) as a transformative strategy in modern clinical practice. However, while FMT is increasingly explored for a diverse range of systemic diseases, its clinical implementation is relatively limited beyond the management of recurrent CDI. This review examines the evolving role of FMT within the therapeutic framework of chronic inflammation, focusing specifically on IBD. We compare the variable clinical outcomes in IBD with the highly successful model of recurrent CDI, highlighting mechanistic and clinical determinants of response in a different disease context. Additionally, we evaluate the progression of delivery strategies, from conventional fecal suspensions to standardized oral capsule formulations, and their implications for efficacy, safety, and scalability. Furthermore, we explore the diversifying clinical scenarios where FMT may be incorporated in the treatment paradigm of IBD, including primary treatment of active inflammation, prevention of relapse, and its place in combination with current immunosuppressive therapies.},
}

@article {pmid42927080,
year = {2026},
author = {Sun, G and Guo, T and Lang, W and Peng, F and Jiang, X and Chen, J},
title = {Global research trends and emerging hotspots in probiotics and children's neurodevelopment: a bibliometric and visualized analysis (1998-2026, partial year).},
journal = {3 Biotech},
volume = {16},
number = {11},
pages = {473},
pmid = {42927080},
issn = {2190-572X},
abstract = {UNLABELLED: Research on the role of probiotics in children's neurodevelopment has expanded rapidly, yet a quantitative synthesis of this interdisciplinary field is lacking. This study aimed to map global research trends, identify key contributors, and reveal emerging hotspots in the field of probiotics and children's neurodevelopment through bibliometric and visualized analysis. Publications indexed in the Web of Science Core Collection from 1998 to 2026 (partial year, search conducted on 21 May 2026) were retrieved using a predefined search strategy combining terms related to probiotics, children, and neurodevelopment. After screening and deduplication, 1,684 documents were included. Bibliometric indicators, including annual publication trends, productive authors and journals, keyword co-occurrence networks, temporal trends in keyword frequency, and the top 15 most frequently cited references, were analyzed using the bibliometrix R package, igraph, ggplot2, and wordcloud. Common keyword synonyms were merged prior to network construction. Annual publication output increased steadily from 1998 to 2015 and accelerated sharply after 2020, reaching a peak in 2025. The most frequent publication venues included Nutrients and Frontiers in Microbiology. Keyword co-occurrence analysis revealed a core network centered on Gut Microbiota, Autism Spectrum Disorder, Probiotics, and Gut-Brain Axis, with ADHD emerging as a distinct and increasingly prominent node in the 2020-2026 period. Temporal trends in keyword frequency indicated a shift from broad descriptive associations toward more specialized terms such as Dysbiosis, Fecal Microbiota Transplantation, Neuroinflammation, and Metabolomics. Highly cited documents and the top 15 most frequently cited references were anchored by seminal works on the gut-brain axis and microbiome-behavior relationships, forming a stable intellectual base. This study provides a comprehensive overview of the research landscape in probiotics and children's neurodevelopment. The field is shifting from observational studies toward mechanism-oriented and interventional research, with ADHD and multi-omics approaches representing important emerging directions. As a single-database analysis, these findings should be interpreted with caution, and future studies should integrate additional databases to validate and extend them. Translational implications include stratifying patients by neurodevelopmental diagnosis and microbial profile, and testing mechanism-guided probiotic or synbiotic formulations in future trials. These findings offer useful guidance for researchers seeking to understand the structure of the field and identify promising areas for future investigation.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05105-2.},
}

@article {pmid42928056,
year = {2026},
author = {Wang, B and Dong, Y and Liu, K and Li, S and Huang, Y and Li, A and Wang, Q and Chen, W and Han, Q and Feng, S},
title = {The Traditional Chinese Medicine-Gut Microbiota-Colorectal Cancer Axis: Mechanistic Insights and Recent Progress.},
journal = {The American journal of Chinese medicine},
volume = {54},
number = {7},
pages = {2123-2164},
doi = {10.1142/S0192415X26500783},
pmid = {42928056},
issn = {1793-6853},
mesh = {Humans ; *Colorectal Neoplasms/microbiology/prevention & control/etiology/drug therapy/metabolism/immunology ; *Gastrointestinal Microbiome/drug effects/physiology ; *Drugs, Chinese Herbal/pharmacology ; *Medicine, Chinese Traditional ; Intestinal Barrier Function ; Dysbiosis ; Tumor Microenvironment ; Animals ; Probiotics ; Epithelial-Mesenchymal Transition/drug effects ; },
abstract = {Colorectal cancer (CRC) remains a leading cause of global cancer mortality, with gut microbiota (GM) dysbiosis playing a critical role in its pathogenesis. Traditional Chinese Medicine (TCM) offers a holistic, multi-target approach and has shown increasing promise in CRC prevention and treatment through GM modulation. This review systematically proposes the "TCM-GM-CRC" axis and elucidates seven interconnected mechanisms through which it mediates the anti-CRC effects of TCM: Reshaping microbial balance by inhibiting pathogens and enriching probiotics; repairing intestinal barrier integrity through upregulation of tight junction proteins and mucin production; suppressing oncogenic and pro-inflammatory signaling pathways by pathogenic bacteria; remodeling the tumor immune microenvironment through immunocyte regulation; modulating microbial metabolites such as short-chain fatty acids, bile acids, and tryptophan derivatives; intervening in CRC cell metabolic reprogramming, including aerobic glycolysis and aberrant lipid metabolism; and inhibiting epithelial-mesenchymal transition and metastasis. Key herbal formulas and active compounds discussed include Canmei Formula, Wu Mei Wan, Gegen Qinlian Decoction, Banxia Xiexin Decoction, and Pien Tze Huang, as well as single compounds such as berberine, evodiamine, curcumin, ginsenoside Rh4, and sophocarpine, which exert anti-CRC effects through distinct GM-mediated pathways. We emphasize the synergistic and multi-dimensional role of TCM in targeting GM and its functional metabolites to combat CRC. To deepen the understanding of the "TCM-GM-CRC" interaction mechanisms, future research should integrate multi-omics technologies, germ-free models, fecal microbiota transplantation, and clinical translation. Additionally, the development of "TCM-plus" combinatorial strategies, microbiota-targeted nanodelivery systems, and medically formulated foods is advocated to advance CRC precision prevention and treatment centered on GM.},
}

Humans
*Colorectal Neoplasms/microbiology/prevention & control/etiology/drug therapy/metabolism/immunology
*Gastrointestinal Microbiome/drug effects/physiology
*Drugs, Chinese Herbal/pharmacology
*Medicine, Chinese Traditional
Intestinal Barrier Function
Dysbiosis
Tumor Microenvironment
Animals
Probiotics
Epithelial-Mesenchymal Transition/drug effects

@article {pmid42929464,
year = {2026},
author = {Yang, J and Zhou, R and Jiang, X and Liu, S and Gu, M and Song, B and Lu, H and Huang, Q and Wang, L and Li, Y and Zuo, L},
title = {Jaceosidin, a Natural Flavonoid From Artemisia argyi, Alleviates Colitis by Remodeling Gut Microbiota to Promote Treg Differentiation via the 5-HIAA-AhR Axis.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {20},
pages = {},
doi = {10.1096/fj.202602971R},
pmid = {42929464},
issn = {1530-6860},
support = {2025byjbgs055//Bengbu Medical University/ ; Byycx25025//Bengbu Medical University/ ; BYYFY2022TD002//Bengbu Medical University/ ; 202427b10020099//Anhui Provincial Research Project/ ; 2022AH020085//Anhui Provincial Research Project/ ; AHWJ2022a019//Anhui Provincial Research Project/ ; 2023AH010067//Anhui Provincial Research Project/ ; },
mesh = {Animals ; *T-Lymphocytes, Regulatory/drug effects/metabolism ; *Colitis/drug therapy/metabolism/chemically induced/microbiology/pathology ; Mice ; *Receptors, Aryl Hydrocarbon/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Cell Differentiation/drug effects ; *Flavonoids/pharmacology ; Male ; Mice, Inbred C57BL ; *Basic Helix-Loop-Helix Proteins/metabolism ; Fecal Microbiota Transplantation ; Indoleacetic Acids/metabolism ; Trinitrobenzenesulfonic Acid/toxicity ; },
abstract = {Dysregulated gut microbiota-immune interactions are increasingly recognized as key contributors to inflammatory bowel disease (IBD), highlighting strategies that restore this crosstalk. Among these, jaceosidin (JAC), a natural flavonoid from Artemisia argyi, represents a potential candidate, and this study investigated its anti-colitis effect and underlying mechanism. TNBS-induced colitis was established in mice, and JAC (10, 20, 40 mg/kg) was administered orally, with 5-ASA as a positive control. Immune cell composition was assessed by flow cytometry. The contribution of the gut microbiota was tested via antibiotic depletion (ABX) and fecal microbiota transplantation (FMT). 16S rDNA sequencing and untargeted metabolomics identified microbial and metabolic changes. The involvement of the aryl hydrocarbon receptor (AhR) pathway was assessed using the AhR antagonist StemRegenin 1 (SR1). JAC dose-dependently alleviated TNBS-induced colitis, with greater improvement at medium and high doses than with 5-ASA under the present experimental conditions; no overt short-term toxicity was observed at the tested doses. Interestingly, JAC increased regulatory T (Treg) cell frequencies in vivo but did not further enhance Treg differentiation in vitro under the tested conditions. ABX attenuated the anti-colitis and Treg-promoting effects of JAC, whereas FMT from JAC-treated donors reproduced these effects, supporting a contribution of the gut microbiota. Fecal supernatants from JAC-treated mice enhanced Treg differentiation under Treg-polarizing conditions, suggesting that soluble fecal factors may contribute to Treg induction. Untargeted metabolomics revealed that JAC markedly altered the fecal tryptophan metabolite profile, with the greatest elevation observed for 5-hydroxyindole-3-acetic acid (5-HIAA) among indole derivatives. Exogenous 5-HIAA alleviated colitis and increased Treg frequencies in vivo, and enhanced Treg differentiation in vitro. Furthermore, both JAC and 5-HIAA increased colonic Cyp1a1 expression, supporting AhR pathway involvement in vivo; pharmacological blockade of AhR attenuated their anti-colitis effects and reduced 5-HIAA-induced Treg differentiation in vitro. JAC alleviates experimental colitis in association with microbiota remodeling and increased fecal 5-HIAA. Exogenous 5-HIAA shows anti-colitis and Treg-promoting activity, supporting further investigation of its contribution to JAC efficacy.},
}

Animals
*T-Lymphocytes, Regulatory/drug effects/metabolism
*Colitis/drug therapy/metabolism/chemically induced/microbiology/pathology
Mice
*Receptors, Aryl Hydrocarbon/metabolism
*Gastrointestinal Microbiome/drug effects
*Cell Differentiation/drug effects
*Flavonoids/pharmacology
Male
Mice, Inbred C57BL
*Basic Helix-Loop-Helix Proteins/metabolism
Fecal Microbiota Transplantation
Indoleacetic Acids/metabolism
Trinitrobenzenesulfonic Acid/toxicity

@article {pmid42930581,
year = {2026},
author = {Wang, Y and Cheng, L and Wang, C and Wang, X and Li, J and Wang, Y and Gao, X and Luo, G},
title = {Re-Du-Ning Alleviates Airway-Intestinal Inflammation of COPD Rats by Regulating Glycerophospholipid Metabolism and Modulating Gut Microbiome.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {6},
pages = {},
doi = {10.3390/medsci14060662},
pmid = {42930581},
issn = {2076-3271},
support = {U21A20407//National Natural Science Foundation of China/ ; 2240STCZB2613//Ministry of Industry and Information Technology/ ; 82003957//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Pulmonary Disease, Chronic Obstructive/drug therapy/metabolism/microbiology ; *Glycerophospholipids/metabolism ; Rats ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Male ; Humans ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Rats, Sprague-Dawley ; },
abstract = {Background: Re-Du-Ning (RDN) is a traditional Chinese medicine (TCM) formulation composed of Lonicera japonica, Gardenia jasminoides, and Artemisia annua. Previous in vitro studies have demonstrated that RDN suppresses pro-inflammatory cytokine release in RAW264.7 macrophages and exhibits potential anti-COPD activity; however, its precise molecular mechanism remains elusive. Methods: A rat COPD model was established by combining cigarette smoke exposure and intratracheal instillation of lipopolysaccharide (LPS). Rats were intragastrically administered with gradient doses of RDN to evaluate its in vivo pharmacological efficacy. Untargeted metabolomics and 16S rRNA microbiome sequencing were performed to screen differential metabolites and gut bacterial genera following RDN intervention, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of core metabolic pathways. Further functional validations were conducted via antibiotic-mediated gut microbiota depletion, fecal microbiota transplantation (FMT), targeted glycerophospholipid supplementation, and human clinical cohort datasets from the Gene Expression Omnibus (GEO) to verify the central roles of gut microbiota and glycerophospholipid metabolism. Results: RDN intervention partially improved lung-function impairment and attenuated histopathological changes in the lung and colon in rats with COPD, while simultaneously reducing the levels of IL-1β, TNF-α, and IL-6 in serum, BALF, and feces. Mult-omics analysis further revealed that RDN partially restored glycerophospholipid metabolic profiles and reshaped gut microbiota composition, and a "host phenotype-metabolite-gut microbiota" network was constructed using correlation analysis. Finally, antibiotic depletion and faecal microbiota transplantation (FMT) experiments suggested that an intact gut microbiota is required for the full protective effect of RDN and that part of this effect is transferable by FMT; LPC (14:0) and LPC (16:0) can regulate cytokine release in BEAS-2B cells, and data from the GEO human cohort further validated the role of glycerophospholipid metabolism in COPD. Conclusions: RDN effectively alleviates symptoms in rats with COPD by regulating the gut microbiota and glycerophospholipid metabolism, providing a comprehensive and in-depth understanding of the multisystem regulatory network underlying COPD.},
}

Animals
*Pulmonary Disease, Chronic Obstructive/drug therapy/metabolism/microbiology
*Glycerophospholipids/metabolism
Rats
*Gastrointestinal Microbiome/drug effects
*Drugs, Chinese Herbal/pharmacology/therapeutic use
Male
Humans
Disease Models, Animal
Fecal Microbiota Transplantation
Rats, Sprague-Dawley

@article {pmid42930589,
year = {2026},
author = {Nassar, SA},
title = {From Dysbiosis to Symbiosis: Using the Gut Microbiome to Improve Cancer Outcomes.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {6},
pages = {},
doi = {10.3390/medsci14060669},
pmid = {42930589},
issn = {2076-3271},
support = {2025/03/37810//Prince Sattam Bin Abdulaziz University/ ; },
mesh = {Humans ; *Symbiosis ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome/physiology ; *Neoplasms/microbiology/therapy ; Animals ; },
abstract = {The gut microbiome has emerged as an important regulator of cancer biology, influencing carcinogenesis, treatment response, and therapy-related toxicity. This narrative review synthesizes current evidence on the mechanistic roles of the gut microbiota in gastrointestinal (GI) cancers and evaluates emerging microbiome-based strategies for improving cancer outcomes. Dysbiosis-characterized by altered microbial diversity, depletion of beneficial functions, and enrichment of disease-associated taxa-may contribute to tumorigenesis through interconnected mechanisms involving chronic inflammation, genotoxicity, metabolic dysregulation, epigenetic alterations, and immune evasion. Key cancer-associated bacteria, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis (ETBF), pks[+]Escherichia coli, and Helicobacter pylori, illustrate the mechanistic diversity of microbiota-associated carcinogenesis. Beyond cancer initiation, the gut microbiome can influence the efficacy and toxicity of anticancer therapies. In immunotherapy, specific microbial taxa and metabolites modulate antitumor immunity and immune checkpoint inhibitor (ICI) responses, while antibiotic-associated dysbiosis has been linked to poorer outcomes. In chemotherapy, microbial metabolism and microbiota-derived metabolites can alter drug efficacy and toxicity, including modulation of 5-fluorouracil (5-FU) activity. Microbiome-based biomarkers show promise for cancer detection and treatment prediction, with fecal microbial signatures, including F. nucleatum, potentially improving colorectal cancer (CRC) screening when incorporated into multimarker strategies. Therapeutic approaches aimed at restoring microbial symbiosis include fecal microbiota transplantation (FMT), which has shown preliminary potential to restore ICI responsiveness in treatment-refractory melanoma, and probiotic interventions, although clinical evidence remains limited. Emerging engineered microbial therapeutics, including tumor-targeting bacteria designed to deliver localized immunostimulatory payloads, are advancing toward clinical translation. Despite substantial progress, important challenges remain, including methodological heterogeneity, lack of standardized protocols, confounding factors, and unresolved safety concerns. Personalized strategies integrating microbial features with host characteristics and treatment context may ultimately enable more effective microbiome-based approaches to improve cancer outcomes.},
}

Humans
*Symbiosis
*Dysbiosis/microbiology
*Gastrointestinal Microbiome/physiology
*Neoplasms/microbiology/therapy
Animals

@article {pmid42925463,
year = {2026},
author = {Çeli̇k, MN and Mohammadzadeh, M and Ahıskalı Öksüz, M and Coşkun Us, N and Ünlü Söğüt, M},
title = {Gut Microbiota in Alzheimer's Disease and Healthy Aging: Mechanisms, Prevention Strategies and Healthcare Burden.},
journal = {Current nutrition reports},
volume = {15},
number = {1},
pages = {},
pmid = {42925463},
issn = {2161-3311},
mesh = {Humans ; *Alzheimer Disease/microbiology/prevention & control/therapy ; *Gastrointestinal Microbiome/physiology ; *Healthy Aging/physiology ; Dysbiosis/microbiology ; Probiotics ; Fecal Microbiota Transplantation ; },
abstract = {PURPOSE OF REVIEW: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline associated with oxidative stress, neuroinflammation, tau neurofibrillary tangles, amyloid-beta plaque deposition, and metabolic dysfunction. Increasing evidence suggests that the gut microbiota plays an important role in AD pathogenesis through the microbiota-gut-brain axis. This review aims to provide a comprehensive overview of the role of the gut microbiota in AD and healthy aging, with a particular focus on microbiota-targeted preventive and therapeutic strategies and their potential to influence disease progression.

RECENT FINDINGS: Recent studies have demonstrated that alterations in gut microbial composition are closely associated with AD. Patients with AD commonly exhibit a reduced abundance of short-chain fatty acid-producing bacteria and an increased prevalence of lipopolysaccharide-producing taxa, supporting a mechanistic link between microbial dysbiosis, systemic inflammation, and neurodegeneration. Emerging evidence indicates that dietary patterns, prebiotics, probiotics, synbiotics, postbiotics, and microbiota-based therapies, including fecal microbiota transplantation (FMT), may beneficially modulate gut microbial composition and influence AD-related pathophysiological processes. In addition, lifestyle factors such as sleep quality and physical activity have been increasingly recognized for their interactions with the gut-brain axis and their potential to affect cognitive health. Current evidence highlights the gut microbiota as a promising therapeutic target in AD prevention and management. Microbiota-directed interventions, together with healthy dietary and lifestyle modifications, may help attenuate neuroinflammation, improve metabolic homeostasis, and delay cognitive decline. Furthermore, given the substantial global economic burden of AD, microbiota-focused preventive strategies may contribute not only to improving clinical outcomes but also to reducing long-term healthcare and societal costs. Future longitudinal and interventional studies are needed to establish causal relationships and determine the efficacy of microbiota-based therapies in AD.},
}

Humans
*Alzheimer Disease/microbiology/prevention & control/therapy
*Gastrointestinal Microbiome/physiology
*Healthy Aging/physiology
Dysbiosis/microbiology
Probiotics
Fecal Microbiota Transplantation

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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