@article {pmid41911988,
year = {2026},
author = {Zhang, XY and Liu, XX and Justine, EE and Xi, ZH and Li, ML and Wang, TS and Jin, CS and Zhang, W and Mi, XJ},
title = {Vinegar-processed Paeonia lactiflora Pall. ameliorates alcoholic liver disease through the modulation of gut microbiota and FXR-FGF15 gut-liver axis.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121593},
doi = {10.1016/j.jep.2026.121593},
pmid = {41911988},
issn = {1872-7573},
abstract = {Paeonia lactiflora Pall. (PR) is a traditional Chinese medicine (TCM) renowned for its actions in nourishing blood and soothing liver. Guided by the theory of "vinegar processing into the liver meridian", vinegar-processed PR (PRV) is clinically preferred for liver diseases owing to its enhanced properties in soothing liver and ameliorating liver injury. Nevertheless, the efficacy differences and underlying mechanisms of PR and PRV against alcoholic liver disease (ALD) remain unclear.

AIM OF THE STUDY: This study aimed to systematically evaluate the efficacy of PR and PRV against ALD, and to elucidate the underlying mechanism of enhanced hepatoprotective effects of PRV from the perspective of the gut-liver axis by multi-omics approaches.

MATERIALS AND METHODS: UHPLC-Q-Exactive Orbitrap mass spectrometry combined with multivariate data analysis was employed to identify the chemical composition of PR and PRV. A Lieber-DeCarli liquid ethanol diet-induced ALD mice model was established in C57BL/6 mice, and the effects of PR and PRV on ALD-related liver injury and steatosis were evaluated using biochemical and histopathological analyses. Alterations of gut microbiota composition and bile acid (BA) profiles were assessed by 16S rRNA gene sequencing and LC-MS/MS, respectively. Furthermore, we conducted quantitative Real Time-PCR and western blotting to determine the mRNA and protein expression levels of Farnesoid X Receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling pathway, respectively, which are involved in BAs metabolism and enterohepatic circulation. Fecal microbiota transplantation (FMT) was utilized to validate the mechanism underlying the enhanced therapeutic efficacy of PRV against ALD.

RESULTS: Vinegar processing significantly altered the phytochemical profile of PR, increasing phenolic acids and specific monoterpene glycosides components. PRV demonstrated superior efficacy over PR in alleviating dyslipidemia, hepatic steatosis, and inflammatory damage, while effectively restoring intestinal barrier integrity and reducing endotoxin translocation. Moreover, PRV modulated the composition of gut microbiota associated with ALD risk, such as Parasutterella, Allobaculum, Paramuribac ulum, and CAG_485. Mechanistically, this microbial restructuring was associated with BA metabolism normalization and intestinal FXR-FGF15 axis activation, which in turn suppressed hepatic Cyp7A1 expression, thereby reducing hepatic cholesterol accumulation and lipogenesis in the ALD model.

CONCLUSION: Our findings indicate that PRV alleviates ALD by restoring BA metabolism and activating the FXR/FGF15 pathway by regulating gut microbiota balance. These findings provide valuable data supporting the vinegar processing efficacy enhancement theory of TCM, thereby facilitating the clinical application of PRV and guiding future drug and dietary supplement development efforts.},
}

@article {pmid41912086,
year = {2026},
author = {Wu, Y and Li, N and Bai, Y and Wang, L and Zhang, Y and Wang, J and Liu, X and Ni, X},
title = {Altered microbiota drive prelimbic cortex suppression and lower pain thresholds after sleep deprivation.},
journal = {Neurochemistry international},
volume = {},
number = {},
pages = {106151},
doi = {10.1016/j.neuint.2026.106151},
pmid = {41912086},
issn = {1872-9754},
abstract = {Sleep disturbances are increasingly recognized as a lifestyle factor for abnormal pain perception. Recent studies highlight the critical role of gut microbiota in maintaining physiological balance and reveal a bidirectional relationship between microbiota alterations, sleep disorders, and pathological pain. This study investigates the potential role of microbiota in linking sleep deprivation to abnormal pain. Using a chronic sleep deprivation (CSD) model in mice, we observed significantly lower pain thresholds compared to controls. Brain-wide functional ultrasound imaging revealed reduced cerebral blood volume responses to pinprick stimulation in the prelimbic cortex (PrL) of CSD mice, indicating decreased neuronal activity during pain processing. This finding was confirmed by fiber photometry of calcium influx and c-Fos staining in the PrL. Importantly, chemogenetic activation of PrL neurons effectively reversed CSD-induced pain hypersensitivity. CSD also caused significant microbiota alterations, including increased diversity and changes in specific genera associated with brain function-related metabolic pathways. Fecal microbiota transplantation (FMT) demonstrated a causal relationship, as control mice that received microbiota from CSD mice developed pain hypersensitivity, whereas CSD mice that received control microbiota exhibited restored pain thresholds Notably, FMT-induced pain behavior changes correlated with PrL activity alterations. Our study indicates that CSD suppresses PrL activity and causes pain hypersensitivity through alterations in gut microbiota. This study emphasizes the gut-brain axis as a critical pathway in the interplay between sleep deprivation and pain regulation.},
}

@article {pmid41903990,
year = {2026},
author = {Gorji, L and Seldomridge, AN and Holder, AM},
title = {Leveraging the Human Microbiome to Improve Immunotherapy Sensitivity.},
journal = {Surgical oncology clinics of North America},
volume = {35},
number = {2},
pages = {285-298},
doi = {10.1016/j.soc.2025.10.007},
pmid = {41903990},
issn = {1558-5042},
mesh = {Humans ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; *Microbiota/immunology ; *Precision Medicine/methods ; Tumor Microenvironment/immunology ; },
abstract = {The human microbiome is composed of distinct microbial communities or ecosystems found throughout the human body, including within unique tumor microenvironments. In this review, we discuss the microbiome's influence on solid tumors, how the microbiome can be modulated to improve response to immunotherapy, and how emerging evidence suggests that microbiome modulation can add to the repertoire of personalized medicine.},
}

Humans
*Immunotherapy/methods
*Neoplasms/therapy/immunology/microbiology
*Microbiota/immunology
*Precision Medicine/methods
Tumor Microenvironment/immunology

@article {pmid41904644,
year = {2026},
author = {Wang, W and Wen, Y},
title = {The role of systemic inflammation in hepatic encephalopathy: advances in inflammatory mechanisms, prevention and treatment research.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2650232},
doi = {10.1080/07853890.2026.2650232},
pmid = {41904644},
issn = {1365-2060},
mesh = {*Hepatic Encephalopathy/therapy/etiology/prevention & control/immunology ; Humans ; Gastrointestinal Microbiome/immunology ; *Inflammation/complications/therapy/immunology ; Ammonia/metabolism ; Animals ; Dysbiosis/complications ; Fecal Microbiota Transplantation/methods ; Liver Cirrhosis/complications ; Hyperammonemia ; Rifaximin/therapeutic use ; Blood-Brain Barrier ; },
abstract = {OBJECTIVES: This review synthesizes current evidence establishing systemic inflammation as a key pathogenic driver in hepatic encephalopathy (HE) beyond hyperammonemia. It does not replace the ammonia hypothesis but rather acts as a critical synergistic factor, modulating and amplifying ammonia neurotoxicity. It further evaluates the mechanisms linking inflammation to HE and the therapeutic advances in inflammation-targeted prevention and treatment strategies.

METHODS: A comprehensive narrative literature review was conducted, analyzing relevant preclinical models and clinical studies. The search and synthesis focused on inflammatory mechanisms in chronic liver disease, gut-liver-brain axis dysfunction, cirrhosis-associated immune dysfunction (CAID), and resulting neuroinflammatory pathways.

RESULTS: Systemic inflammation, driven by gut dysbiosis, barrier failure, and CAID, amplifies ammonia neurotoxicity and independently contributes to neuroinflammation, blood-brain barrier disruption, and cerebral metabolic dysfunction in HE. Key inflammatory markers, such as IL-6, correlate with disease severity. Therapies targeting inflammation - particularly gut microbiota modulation with rifaximin and fecal microbiota transplantation (FMT) - demonstrate significant efficacy in reducing HE recurrence, lowering systemic inflammation, and improving cognitive outcomes. Other approaches, including albumin infusion, also show promise.

CONCLUSIONS: Systemic inflammation is a pivotal and synergistic factor in HE pathogenesis. Combining anti-inflammatory strategies that target the gut-liver-brain axis with traditional ammonia-lowering therapies offers a more comprehensive and effective treatment paradigm. Future research should prioritize protocol optimization, long-term safety assessment, and the development of personalized treatment approaches.},
}

*Hepatic Encephalopathy/therapy/etiology/prevention & control/immunology
Humans
Gastrointestinal Microbiome/immunology
*Inflammation/complications/therapy/immunology
Ammonia/metabolism
Animals
Dysbiosis/complications
Fecal Microbiota Transplantation/methods
Liver Cirrhosis/complications
Hyperammonemia
Rifaximin/therapeutic use
Blood-Brain Barrier

@article {pmid41907211,
year = {2026},
author = {Li, H and Shen, X and Lu, H},
title = {The Evolving Research Landscape of Radiation Enteritis Prevention and Management: A Data-Driven Analysis.},
journal = {Journal of inflammation research},
volume = {19},
number = {},
pages = {581527},
pmid = {41907211},
issn = {1178-7031},
abstract = {OBJECTIVE: Radiation enteritis (RE) is a common complication following radiotherapy, adversely affecting patient prognosis and quality of life. This study aims to analyze the evolving research landscape of RE prevention and management through a data-driven approach, aiming to delineate the developmental trajectory, identify research hotspots and emerging frontiers, and forecast future trends in RE prevention and management.

METHODS: We conducted a data-driven analysis of relevant publications retrieved from the Web of Science Core Collection (2005-2024). Visualization tool was employed to examine collaboration networks, research hotspots, and trends. A supplementary search in PubMed was conducted to identify related clinical trials.

RESULTS: A total of 594 publications indexed in the Web of Science Core Collection were subjected to a data-driven visual analysis, while a supplementary search in PubMed identified 51 clinical trials to further clarify clinical research status. In this field, the main research topics include prostate cancer, rectal cancer, and cervical cancer, and the main research hotspots include studies on the pathological mechanism of RE, as well as research on the application of conformal radiotherapy, argon plasma coagulation, hyperbaric oxygen therapy, and microbiota transplantation in the prevention and management of RE. Early burst keywords mainly include "conformal radiotherapy", "sucralfate", "home parenteral nutrition", "intensity modulated radiotherapy", and "hyperbaric oxygen therapy". In the past three years, the burst keywords in the outbreak period mainly include "efficacy", "chemoradiation", "stem cells", and "transplantation".

CONCLUSION: This study reveals that the field has gradually shifted over the past two decades from an initial focus on pathological mechanisms and symptom management toward etiological therapy, with current research frontiers centered on therapies such as mesenchymal stem cell therapy and fecal microbiota transplantation. Future efforts should be guided by this paradigm shift, prioritizing the resolution of specific translational challenges inherent to these emerging treatments, fostering the multidisciplinary collaboration essential in clinical practice, and advancing toward more predictive, preventive, and personalized management strategies for RE. These findings provide valuable insights and guidance for future clinical research and innovation in this field.},
}

@article {pmid41907468,
year = {2026},
author = {Gao, Y and Yang, D and Wang, D and Maimaiti, R},
title = {Behavioral and biological alterations following transplantation of ASD-associated gut microbiota in mice.},
journal = {PeerJ},
volume = {14},
number = {},
pages = {e20951},
pmid = {41907468},
issn = {2167-8359},
mesh = {Animals ; *Gastrointestinal Microbiome ; *Autism Spectrum Disorder/microbiology/therapy/psychology ; Mice ; *Fecal Microbiota Transplantation ; Male ; *Behavior, Animal ; RNA, Ribosomal, 16S/genetics ; Hippocampus/metabolism/pathology ; Female ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; T-Lymphocytes, Regulatory ; },
abstract = {BACKGROUND: Alterations in the gut microbiota have been increasingly reported in individuals with autism spectrum disorder (ASD). However, the extent to which ASD-associated microbial communities are linked to behavioral and host biological changes remains to be clarified.

METHODS: Fecal microbiota transplantation (FMT) was performed using samples from children with ASD or typically developing (TD) controls into antibiotic-pretreated mice. Behavioral performance was evaluated using open field, social interaction, and spatial learning paradigms. Gut microbial composition was assessed by 16S rRNA gene sequencing. Peripheral immune-related parameters were assessed, including circulating regulatory T cells and serum cytokine profiles. Histological and molecular analyses were conducted in the terminal ileum and hippocampus, including immunohistochemistry, Western blotting, exploratory brain proteomics, and targeted qRT-PCR validation.

RESULTS: Mice receiving ASD-associated microbiota displayed altered behavioral performance, including reduced sociability and impaired spatial learning. 16S rRNA sequencing revealed distinct gut microbial profiles between ASD-FMT and TD-FMT groups, with increased abundance of Enterobacteriaceae and related taxa in ASD-FMT mice. Peripheral analysis showed reduced regulatory T cell levels and altered serum cytokine profiles. Histological examination identified changes in intestinal architecture and increased expression of glial markers in the hippocampus. Proteomic analysis indicated differential expression of proteins enriched in pathways related to neural structural organization and metabolic processes.

CONCLUSIONS: These findings indicate that gut microbiota derived from children with ASD is associated with coordinated behavioral, peripheral immune-related, and brain histological changes in mice. This study provides integrative evidence supporting associations between ASD-associated microbial features and coordinated behavioral and biological alterations in the host.},
}

Animals
*Gastrointestinal Microbiome
*Autism Spectrum Disorder/microbiology/therapy/psychology
Mice
*Fecal Microbiota Transplantation
Male
*Behavior, Animal
RNA, Ribosomal, 16S/genetics
Hippocampus/metabolism/pathology
Female
Mice, Inbred C57BL
Humans
Disease Models, Animal
T-Lymphocytes, Regulatory

@article {pmid41907523,
year = {2026},
author = {Fernanda Ricci, M and Cruz, CS and de Almeida, VM and d' Auriol, M and Rocha, VM and Machado, EC and Gallotti, B and Garbazza, I and Faria, AMC and Cassali, GD and Garcia, CC and André, LC and Martins, FS and Abreu, V and Almeida, S and Vieira, AT},
title = {Fiber-deprived diet weakens lung defense against antimicrobial-resistant Klebsiella pneumoniae and facilitates resistance phenotype in the gut microbiota.},
journal = {Gut microbes reports},
volume = {3},
number = {1},
pages = {2625617},
pmid = {41907523},
issn = {2993-3935},
abstract = {The rapid spread of antimicrobial-resistant (AMR) bacteria is a major global health challenge. The misuse of antibiotics and infections by resistant pathogens drive the dissemination of resistance genes, the human microbiota of which serve as reservoirs. Disruptions in the host-microbiota balance, which are influenced by diet, can increase resistance genes. Low-fiber diets are linked to gut dysbiosis, infection susceptibility, and weakened defenses. Here, we report that dietary fiber deprivation induced significant alterations in the gut microbiota of C57BL/6 mice, leading to reduced host tolerance to lung infection by the AMR strain Klebsiella pneumoniae B31 (KP 31) with higher levels of ampicillin-resistant Enterobacteriaceae and marked shifts in the gut microbial composition. Germ-free mice that received fecal transplants from fiber-deprived donors also displayed exacerbated inflammatory pathology following KP 31 infection. Infection further increased the abundance of cultivable resistant Enterobacteriaceae in the gut and was associated with the modulation of short-chain fatty acid (SCFA) levels, particularly propionate. Propionate appears to support antimicrobial activity, and its decrease in vitro promotes bacterial growth. Our findings highlight that the gut microbiota is a crucial reservoir for resistance genes. Low-fiber diets impair lung defenses and promote resistome expansion after AMR infection. Understanding these dynamics and their influencing factors is essential for strategies to combat antimicrobial resistance (AMR).},
}

@article {pmid41908202,
year = {2026},
author = {Awashra, A and Neiroukh, H and AbuBaha, M and Shehadeh, W and Jallad, H and Emara, A and Abu-Khazneh, O and Zahran, A and Elgendy, MS and Fkheideh, T and Sawaftah, Z and Milhem, F and Hajjeh, O and Shubietah, A},
title = {The gut-heart axis in atrial fibrillation: Pathophysiology, evidence, and therapeutic potential.},
journal = {Heart rhythm O2},
volume = {7},
number = {3},
pages = {581-597},
pmid = {41908202},
issn = {2666-5018},
abstract = {BACKGROUND: Recent advances in microbiome research highlight a bidirectional relationship between gut microbiota and atrial fibrillation (AF), the most common sustained arrhythmia worldwide. Gut dysbiosis has been implicated in systemic inflammation, metabolite imbalance, bile acid signaling, and autonomic dysfunction, whereas AF itself alters microbial homeostasis through hemodynamic and neurohormonal changes.

OBJECTIVE: This review aimed to synthesize current evidence linking gut dysbiosis to AF pathogenesis, identify mechanisms underlying this interaction, and explore the therapeutic potential of microbiota-targeted interventions.

METHODS: We conducted a narrative review of preclinical, clinical, and epidemiologic studies examining the gut-heart axis in AF. Particular emphasis was placed on microbial metabolites (eg, trimethylamine N-oxide, short-chain fatty acids, indoxyl sulfate), bile acid modulation, and inflammatory signaling. Data on interventions, including diet, probiotics, pharmacologic approaches, and fecal microbiota transplantation, were integrated to assess translational potential.

RESULTS: Evidence suggests that gut-derived signals contribute to atrial remodeling through activation of the NLRP3 inflammasome, altered calcium handling, and impaired gap junction integrity. Conversely, AF promotes dysbiosis by reducing gut perfusion, altering motility, and exposing patients to polypharmacy. Microbiota-directed strategies, particularly dietary modification and probiotics, demonstrate promise in reducing arrhythmic risk, whereas early data indicate potential biomarker roles for gut microbial signatures in AF stratification. However, causality remains uncertain, given that most studies are observational with limited sample sizes.

CONCLUSION: The gut-heart axis represents a novel paradigm in AF research. Although preliminary findings support its mechanistic and therapeutic relevance, interventional studies are needed to establish causality and guide clinical application.},
}

@article {pmid41908827,
year = {2026},
author = {Yang, X and Niu, R and Lan, T and Ren, S and Liang, H and Ma, Y and Liu, C},
title = {Traditional Chinese medicine and plant metabolites for rheumatoid arthritis via modulating gut microbiota: a scoping review evaluating the transition from correlation to causality.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1790536},
pmid = {41908827},
issn = {1663-9812},
abstract = {BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis. The "gut-joint axis" proposes gut microbiota and metabolites modulate RA inflammation via mucosal and systemic immune responses. Botanical drugs (Traditional Chinese Medicine, TCM) and plant metabolites offer multi-target potential. However, most studies remain descriptive, demonstrating concurrent microbial shifts but lacking causal designs to verify mechanistic necessity.

OBJECTIVES: This scoping review examines TCM and plant metabolite interventions on RA gut microecology (2015-2025), focusing on the "microbiota-metabolite-immune" axis. It aims to classify evidence based on causal design rigor and identify steps to advance research from correlation to causality.

METHODS: We searched PubMed, Embase, and Web of Science (2015-2025). Studies reporting RA outcomes and gut microbiota changes following TCM interventions were included. We established a hierarchical classification system based on design rigor: antibiotic depletion (ABX), fecal microbiota transplantation (FMT), metabolite rescue, and blocking. Evidence was stratified: Level A (Closed-loop: ABX + FMT + rescue/blocking), Level A+ (plus in vitro blocking), Level B (Partial: ABX/FMT alone), and Level C (Correlational).

RESULTS: Of 25 included studies (24 animal, 1 clinical), only 2 were Level A, 1 Level A+, 3 Level B, and 19 Level C. While TCM improved RA phenotypes and altered microbiota, complete closed-loop verification remains rare. Short-chain fatty acids (SCFAs) show promise but inconsistent trends due to heterogeneity. Bile acids and tryptophan metabolites correlate with reduced inflammation, yet their mechanistic necessity remains largely untested.

CONCLUSION: Botanical drugs and plant metabolites demonstrate potential in modulating gut microbiota to improve RA. However, definitive causal links remain underexplored. Future research should prioritize "shortest closed-loop" strategies, including targeted quantification, rescue, and necessity validations. Longitudinal designs and systemic immune metrics are essential to transition from correlations to translatable mechanisms.},
}

@article {pmid41908832,
year = {2026},
author = {Zhao, S and Tan, Z and Suo, J and Bu, Y},
title = {Lycium barbarum polysaccharides as prebiotics prevent colorectal cancer liver metastasis in non-alcoholic fatty liver disease by modulating gut microbiota-FGF21-PI3K-AKT axis.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1735434},
pmid = {41908832},
issn = {1663-9812},
abstract = {INTRODUCTION: Colorectal cancer liver metastasis (CRLM) is the leading cause of death in colorectal cancer, and nonalcoholic fatty liver disease (NAFLD) promotes CRLM. Lycium barbarum polysaccharides (LBPs), bioactive metabolites of the traditional medicinal plant Lycium barbarum L, inhibit the progression of colorectal cancer and NAFLD by regulating gut microbiota composition. However, their roles in preventing CRLM under NAFLD conditions remain unclear. This study aimed to investigate the preventive effect of LBPs on liver metastasis of colorectal cancer in the context of NAFLD and explore its potential mechanisms.

METHODS: An NAFLD mouse model was established, followed by prophylactic oral administration of LBPs by gavage for 28 days before splenic injection of MC38 colorectal cancer cells to establish liver metastasis. Pseudo-germ-free mice combined with fecal microbiota transplantation were constructed to explore the role of the gut microbiota in the preventive effect of LBPs on CRLM. Gut microbiota and fecal short-chain fatty acids were analyzed by 16S rRNA sequencing and liquid chromatography-mass spectrometry. Spearman's correlation analysis was used to explore the correlation between bacterial genera and liver lipid metabolism indicators. Serum non-targeted metabolomic profiling and transcriptomic analysis of CRLM cells were performed to elucidate metabolic and molecular mechanisms.

RESULTS: Under NAFLD conditions, LBPs markedly reduced hepatic metastatic burden, liver weight, and liver-to-body weight ratio. LBPs ameliorated hepatic lipid metabolism and restored colonic barrier integrity in NAFLD mice. The gut microbiota was identified as a critical mediator of LBPs-induced protection against CRLM, and depletion of the microbiota completely abrogated the anti-metastatic effects of LBPs. LBPs enhanced microbial diversity and richness, enriched of short-chain fatty acid-producing bacterial genera, such as Cryptobacteroides, Evtepia, and Bacteroides-H, and elevated colonic butyrate levels. Metabolomic profiling revealed reduced serum acylcarnitines and increased organic acids. Transcriptomic profiling showed upregulation of fibroblast growth factor 21, activation of the PI3K-AKT signaling pathway, and promotion of epithelial-mesenchymal transition in colorectal cancer cells, while LBPs reverse these changes.

DISCUSSION: LBPs prevent CRLM associated with NAFLD by modulating the gut microbiota, enhancing butyrate production, improving hepatic metabolic homeostasis, and suppressing prometastatic signaling pathways. These findings highlight LBPs as promising preventive agents against CRLM in the setting of metabolic liver disease.},
}

@article {pmid41909032,
year = {2026},
author = {Yu, Z and Ma, H and Zhang, H and Gao, L and Fu, X and Wang, H and Xiao, Y and Wu, X and Zhang, A and Kang, Y and Cui, G and Chen, Z and Wu, D},
title = {Gut microbiota mediates the anti-obesity effects of Gnaphalium affine methanol extract in HFD-induced obesity.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1779459},
pmid = {41909032},
issn = {2296-861X},
abstract = {BACKGROUND: Obesity constitutes a pressing global public health challenge, characterized by intricate associations with metabolic dysregulation and gut microbiota dysbiosis.

METHODS: This study systematically evaluated the anti-obesity efficacy and underlying mechanisms of Gnaphalium affine methanol extract (GAE) in high-fat diet (HFD)-induced obese mice, with integrated fecal microbiota transplantation (FMT) experiments to establish causal relationships between GAE-modulated gut microbiota and metabolic improvements.

RESULTS: GAE intervention significantly ameliorated HFD-induced metabolic disorders, as evidenced by reduced oxidative stress, enhanced glucose tolerance, suppressed visceral adiposity, and attenuated chronic low-grade inflammation. Mechanistically, GAE preserved intestinal barrier integrity through upregulation of tight junction protein expression. Multi-omics integration of 16S rRNA gene sequencing and untargeted metabolomics revealed that GAE substantially rectified gut microbiota dysbiosis and lipid metabolic disturbances, mediated by specific bioactive metabolites-including lysophosphatidylcholine 22:6 and N-oleoyl glycine-and enrichment of beneficial bacterial genera (Phascolarctobacterium and Lactobacillus). Critically, FMT experiments demonstrated that the gut microbiota remodeled by GAE administration was sufficient to transfer obesity-alleviating phenotypes to recipient mice.

CONCLUSION: Collectively, these findings establish that GAE exerts multi-target anti-obesity effects through modulation of the "microbiota-gut-metabolism" axis, providing compelling preclinical evidence supporting the development of GAE as a functional food ingredient for weight management applications.},
}

@article {pmid41909046,
year = {2026},
author = {Song, Y and Liu, G and Yang, J and Wang, J and Feng, S and Lu, S and Qin, Z and He, X and Wu, L},
title = {The impact of washed microbiota transplantation on serum gastric function markers: pepsinogen I, pepsinogen II, and Gastrin-17.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1715003},
pmid = {41909046},
issn = {2296-861X},
abstract = {BACKGROUND AND AIMS: Conventional treatment methods for gastric diseases have problems such as drug resistance and recurrence. This study aims to explore whether a new treatment method-Washed Microbiota Transplantation (WMT)-can improve gastric mucosal health.

METHODS: The clinical data of patients before and after WMT treatment were collected and analyzed, including serum gastric function markers: gastrin-17 (G-17), pepsinogen I (PGI), pepsinogen II (PGII), and the PGI/PGII ratio (PGR). Inflammatory biomarkers: C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). Fresh fecal samples were collected at baseline and after WMT treatment and stored at -80 °C until analysis. Gut microbiota profiling was performed using 16S rRNA genes sequencing. Gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale (GSRS), and health-related quality of life assessed by the SF-36 physical and mental component summaries (PCS and MCS). The safety and tolerability of WMT were also assessed.

RESULTS: After WMT treatment, serum G-17 and PGI levels decreased significantly within the WMT group (both p < 0.05), while PGII demonstrated a downward trend. Notably, in between-group comparisons, only the change in G-17 showed a statistically significant advantage over the control group (p = 0.032), whereas differences in PGI, PGII, and PGR were not significant. Inflammatory markers CRP and PCT likewise declined within the WMT group; notably, the magnitude of CRP reduction positively correlated with changes in PGI (r > 0.5, p < 0.01). Furthermore, 16S rRNA sequencing revealed a significant increase in gut microbial α-diversity following WMT, with Chao1, Shannon, and Simpson indices all significantly elevated after the second treatment course compared with baseline (p < 0.05); the relative abundances of several key genera were significantly altered. In addition, patients exhibited significant improvement in GSRS scores (p < 0.01), and both SF-36 PCS and MCS scores increased markedly compared to baseline (p < 0.01). No serious adverse events were observed during the study period; a minority of patients reported mild, transient bloating or diarrhea.

CONCLUSION: WMT was associated with improvements in gastric mucosal health, gut microbial abundance and diversity, accompanied by reduced inflammation, alleviated gastrointestinal symptoms, improved quality of life, and a favorable safety profile.},
}

@article {pmid41909260,
year = {2026},
author = {Wang, XL and Zhang, C and Lu, DS and Dong, ZY and Jin, BM and Wan, SY and Zhang, ZW and Zhang, CJ and Li, L},
title = {Paeoniflorin protects against NAFLD through antioxidant, anti-inflammatory effects and restoration of gut microbiota homeostasis.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1766068},
pmid = {41909260},
issn = {1664-302X},
abstract = {Non-alcoholic fatty liver disease (NAFLD) is a widespread chronic metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, inflammation and gut dysbiosis. Paeoniflorin (PAF) exhibits potential against NAFLD, yet its antioxidant mechanism via the gut-liver axis remains unclear. In a high-fat/sucrose (HFS) diet-induced NAFLD mouse model, C57BL/6 mice received PAF (50 or 100 mg/kg/day) for 10 weeks. Oxidative stress markers, histopathology, gut microbiota, and serum metabolomics were conducted, with fecal microbiota transplantation (FMT) applied for causal validation. PAF ameliorated metabolic disorders by suppressing hepatic lipogenesis and promoting cholesterol excretion. PAF significantly ameliorated oxidative stress by enhancing hepatic and colonic anti-oxidant capacity, evidenced by increased SOD activity and decreased MDA levels. It concurrently reduced systemic inflammation and enhanced intestinal barrier integrity via upregulation of tight junction proteins. Furthermore, PAF reshaped the gut microbiota, elevating beneficial Akkermansia and microbial-derived SCFAs, while suppressing pro-oxidant and pro-inflammatory pathogens like Desulfovibrio and Helicobacter. FMT confirmed that these antioxidant and metabolic benefits were mediated by the gut microbiota. In conclusion, PAF alleviates NAFLD primarily through potent antioxidant actions and anti-inflammatory, achieved via remodeling gut microbial ecology and reinforcing intestinal barrier.},
}

@article {pmid41909883,
year = {2025},
author = {Abubakar, D and Abdullahi, H and Ibrahim, I},
title = {Bridging Microbiomes: Exploring Oral and Gut Microbiomes in Autoimmune Thyroid Diseases- New Insights and Therapeutic Frontiers.},
journal = {Gut microbes reports},
volume = {2},
number = {1},
pages = {2452471},
pmid = {41909883},
issn = {2993-3935},
abstract = {Autoimmune thyroid diseases (AITDs) are the most common organ-specific autoimmune disorders characterized by thyroid dysfunction and immune system deficiencies. In recent decades, the role of the microbiome in autoimmune diseases has gained increasing attention, with emerging research linking gut microbiome alterations to the development of AITDs. This review summarizes current knowledge on the relationship between AITDs and the gut microbiome. Additionally, it emphasizes the role of the oral microbiome in AITDs, an area often overlooked in autoimmune research. Beyond the microbiome, the virome and mycobiome have been recognized as critical but underexplored components of the human microbiome, potentially contributing to immune dysregulation and the pathogenesis of AITDs. The review also explores modulating the microbiome for managing AITDs, including diet adjustment, the potential use of probiotics, postbiotics, symbiotics, and even fecal microbiota transplantation (FMT) to restore a balanced microbiome that may positively influence the immune system and, by extension, the course of AITDs. This review thoroughly explores the intricate relationship between AITDs, the gut, and oral microbiomes, paving the way for precision medicine applications in AITDs. Examining microbiota-thyroid interactions highlights the potential for targeted, personalized treatments and novel therapeutic therapies, guiding future therapeutic strategies for more effective and precisely tailored AITD management approaches.},
}

@article {pmid41909892,
year = {2025},
author = {Montenegro-Borbolla, E and Wakim El-Khoury, J and Bertelli, C and Schoepfer, A and Guery, B and Galperine, T},
title = {Resolution of long-term severe irritable bowel syndrome following fecal microbiota transplantation: A case report and microbiota analysis.},
journal = {Gut microbes reports},
volume = {2},
number = {1},
pages = {2487905},
pmid = {41909892},
issn = {2993-3935},
abstract = {The diagnosis and management of irritable bowel syndrome (IBS) is challenging due to its complex symptoms and inconsistent treatment responses. Given the important role of gut microbiota in gastrointestinal health, fecal microbiota transplantation (FMT) is a promising intervention. We describe the case of a 55-y-old woman without prior gastrointestinal issues who, following severe depression, developed multiple gastrointestinal symptoms, including abdominal pain, fluctuating bowel habits, and a persistent burning sensation in her mouth and upper gastrointestinal tract. At Lausanne University Hospital, she was diagnosed with IBS resistant to multiple lines of treatment and a multidisciplinary team proposed multiple oral FMTs. One-month post-FMT, her gastrointestinal symptoms significantly improved and remained better after a year, with only the burning sensation persisting. Analysis of pre- and post-FMT samples and donor material, using 16S rRNA amplicon metagenomics, revealed a 90% genus-level taxonomic overlap between the patient and the donor. The observed changes in the relative abundance of these genera, including the enrichment of beneficial gut commensals, as well as the elimination of IBS-associated genera likely supported her recovery. Overall, FMT led to substantial improvement in her long-standing gastrointestinal symptoms.},
}

@article {pmid41910195,
year = {2026},
author = {Jia, PP and Li, Y and Yang, HY and Ding, Y and Guo, FY and Wu, MF and Jia, JQ and Pei, DS},
title = {Fecal microbiota transplantation and Akkermansia muciniphila restore neurodevelopment and behavior via the gut-brain axis in autism-like zebrafish.},
journal = {The ISME journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/ismejo/wrag074},
pmid = {41910195},
issn = {1751-7370},
abstract = {Effective therapies for Autism Spectrum Disorder (ASD) are currently limited, and the functional connections between gut microbiota and brain development are not fully elucidated. Using the Katnal2 mutant zebrafish as an ASD-like model, we evaluated whether fecal microbiota transplantation (FMT) from wild-type donors or supplementation with the probiotic Akkermansia muciniphila (A. muciniphila) could ameliorate neurodevelopmental deficits. Assessments included developmental phenotypes, behavior, microbial profiling, neurotransmitter-related gene expression, and short-chain fatty acid (SCFA) signaling in conventionally reared (CR) and germ-free (GF) fish. FMT from wild-type donors and A. muciniphila supplementation significantly improved hatching rates, growth parameters, heart rate, and locomotor activity in Katnal2 mutants, whereas microbiota from Katnal2 mutants induced analogous deficits in wild-type recipients. A. muciniphila successfully colonized the gut, reshaped microbial communities, and reduced anxiety-like behaviors. Mechanistically, A. muciniphila upregulates genes involved in dopamine (th), serotonin (tph1a), and gamma-aminobutyric acid (GABA) synthesis, downregulates the serotonin receptor htr3a, and enhances expression of the SCFA receptor ffar2, independently of total SCFA levels. Correlation analyses linked key developmental, behavioral, and transcriptional changes to altered microbial genera in a sample-specific manner, highlighting compositionally driven neuromodulatory effects of genetic and probiotic interventions. Thus, microbiota-targeted intervention with A. muciniphila rescues neurodevelopmental impairments in ASD models by remodeling the gut-brain axis, supporting its translational potential.},
}

@article {pmid41910214,
year = {2026},
author = {Zhang, F and Xu, W and Zeng, R and Chen, J and Huang, J},
title = {Limosilactobacillus reuteri normalizes gut microbiota dysfunction and social deficits of rat offspring associated with prenatal exposure to stress.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2649440},
doi = {10.1080/19490976.2026.2649440},
pmid = {41910214},
issn = {1949-0984},
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; Pregnancy ; *Limosilactobacillus reuteri/physiology ; Rats ; *Prenatal Exposure Delayed Effects/microbiology ; Male ; Social Behavior ; Oxytocin/metabolism ; Fecal Microbiota Transplantation ; *Stress, Psychological/microbiology ; Rats, Sprague-Dawley ; *Probiotics/administration & dosage ; Paraventricular Hypothalamic Nucleus/metabolism ; Behavior, Animal ; },
abstract = {Prenatal stress (PS) is a potential risk factor for social behavior impairment in offspring. Here, we demonstrate that PS induces gut microbiota alterations that are associated with impaired sociability and social novelty preference in rat offspring. In addition, we found that these behavioral deficits could be partially rescued through either cohousing with normal offspring or fecal microbiota transplantation from control donors. Metagenomic analysis identified Limosilactobacillus reuteri (L. reuteri) as a key species based on the considerable difference in its abundance between the PS and control offspring. Subsequent investigations revealed that supplementing L. reuteri during critical neurodevelopmental windows restored oxytocin levels in the paraventricular nucleus (PVN) and rescued dopamine reward pathway function, thereby ameliorating PS-induced social deficits. Notably, these beneficial effects were completely abolished by either treatment with an oxytocin receptor antagonist or subdiaphragmatic vagotomy. Thus, both oxytocin signaling and vagal afferent pathways play essential roles in the observed benefits of L. reuteri. Our findings indicate that social behavior impairments in offspring exposed to prenatal maternal stress can be explained by a novel mechanism involving the gut microbiota-brain axis: whereby PS-induced depletion of specific commensal bacteria (particularly L. reuteri) disrupts vagus nerve-mediated oxytocinergic modulation of PVN-to-VTA dopaminergic circuits, ultimately leading to social behavior impairments in offspring.},
}

Animals
*Gastrointestinal Microbiome/physiology
Female
Pregnancy
*Limosilactobacillus reuteri/physiology
Rats
*Prenatal Exposure Delayed Effects/microbiology
Male
Social Behavior
Oxytocin/metabolism
Fecal Microbiota Transplantation
*Stress, Psychological/microbiology
Rats, Sprague-Dawley
*Probiotics/administration & dosage
Paraventricular Hypothalamic Nucleus/metabolism
Behavior, Animal

@article {pmid41724956,
year = {2026},
author = {Xu, Y and Huang, L and Sun, L and Li, C and Zhou, C and Liu, P and Zhang, Z and Deng, S and Mao, C and Hu, Z and Bao, X and Xia, S and Xu, Y},
title = {Gut Lachnospiraceae improves white matter injury-related cognitive decline by increasing L-arginine.},
journal = {Cellular & molecular biology letters},
volume = {31},
number = {1},
pages = {},
pmid = {41724956},
issn = {1689-1392},
support = {82130036/823B2027//National Natural Science Foundation of China/ ; 2022ZD0211800//STI2030-Major Projects/ ; ZDXK202216//Jiangsu Province Key Medical Discipline/ ; },
abstract = {BACKGROUND: White matter injury (WMI) is the most prevalent lesion in cerebral small vessel disease and a major contributor to cognitive decline. Recent studies have highlighted the critical role of gut microbiota in regulating brain disorders. However, the role of gut microbiota in WMI-related cognitive decline remains unclear.

METHODS: A bilateral carotid artery stenosis (BCAS) mouse model was established to mimic WMI and related cognitive decline. Fecal microbiota transplantation was employed to verify the causal relationship between gut microbiota dysbiosis and WMI. 16 S rRNA gene sequencing was used to analyze gut microbiota and its potential functions. Untargeted metabolomics was applied to identify differential metabolites. Cognitive function was assessed through Y-maze, novel object recognition, and fear conditioning tests. WMI was assessed using in vivo imaging, immunostaining, and electron microscopy. The changes in oligodendrocyte lineage cells, microglia, and blood-brain barrier were investigated using immunofluorescence staining, EdU cell proliferation assays, and Western blotting. Patients with ischemic WMI were included to examine the correlation between serum L-arginine (L-Arg) levels, brain imaging, and cognition.

RESULTS: We discovered that BCAS mice exhibited gut microbiota dysbiosis and reduced arginine biosynthesis, with decreased L-Arg levels in serum and white matter. Fecal microbiota from BCAS mice resulted in WMI and related cognitive decline in normal mice. Serum L-Arg levels were reduced in patients with ischemic WMI and were closely associated with WMI and cognitive decline. Importantly, L-Arg supplementation improved WMI-related cognitive decline in BCAS mice. Mechanistically, L-Arg promoted oligodendrocyte precursor cell proliferation and differentiation, enhanced the anti-inflammatory activity of microglia, and reduced blood-brain barrier leakage, thereby mitigating WMI-related cognitive decline. Furthermore, Lachnospiraceae was identified as the main source of gut-to-brain L-Arg. Supplementation with Lachnospiraceae alleviates WMI-related cognitive decline.

CONCLUSION: Overall, our study revealed the critical role of gut microbiota, particularly Lachnospiraceae, and L-Arg in improving WMI-related cognitive decline, providing novel strategies for understanding and treating WMI-related cognitive decline.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11658-026-00866-3.},
}

@article {pmid41794382,
year = {2026},
author = {Lowry, DE and Cho, NA and Sampsell, K and Sales, KM and Noye Tuplin, EW and Biddle, M and Wang, W and Chleilat, F and Chow, MR and Buzatto, AZ and Reimer, RA},
title = {Prebiotics partially protect offspring from maternal antibiotic-induced obesity risk by altering maternal milk microbiota and gut colonization in Sprague-Dawley rats.},
journal = {The Journal of nutritional biochemistry},
volume = {153},
number = {},
pages = {110337},
doi = {10.1016/j.jnutbio.2026.110337},
pmid = {41794382},
issn = {1873-4847},
abstract = {Maternal antibiotic use can increase obesity risk in offspring. Co-administering prebiotics mitigates the risk in rats. How prebiotics and antibiotics interact to affect obesity risk is unknown, but could involve altered milk microbiota that influences offspring gut colonization. Sprague-Dawley rat dams were exposed to antibiotics (low-dose penicillin) and/or prebiotics (oligofructose) during gestation and lactation. Gut and milk microbiota were measured using 16S rRNA sequencing, and metabolic measurements were taken for dams and offspring at weaning (day 21) and 10 days postweaning (day 31). Germ-free mice were transplanted with maternal cecal microbiota to assess the causal role of vertically transmitted microbiota. Offspring maternally exposed to antibiotics showed relatively accelerated taxonomic maturation in the gut pre- and postweaning. Milk composition (fat, protein, hormone, microRNA, and cytokines) was unchanged, but milk-derived bacteria differed between maternal treatments and contributed to offspring gut microbial structure. Male offspring were especially affected by maternal antibiotic exposure and had increased body weight, fat mass, caloric intake, and hepatic triglycerides by day 31. All but hepatic triglycerides were attenuated with maternal prebiotic coconsumption. fecal microbiota transplants of maternal cecal matter into germ-free mice replicated male offspring body weight and hepatic outcomes. Untargeted hepatic lipidomics and network analysis revealed strong connections between several bacteria and lipid species potentially of bacterial origin that were enriched in prebiotic offspring microbiota and livers. These data confirm the role of milk microbiota in seeding offspring microbiota and implicate maternal antibiotic-associated gut microbiota as causally implicated in compromising early-life offspring hepatic metabolism that may lead to later metabolic disorders.},
}

@article {pmid41902480,
year = {2026},
author = {Chugh, RM and Bhanja, P and Schueddig, E and Setianegara, J and Lin, Y and Guida, K and Rehman, S and Krepel, S and Koestler, D and Chen, RC and Cook, KL and Saha, S},
title = {Proton FLASH Exposure Preserves Gut Commensal Microbiomes and Spares Intestinal Stem Cells.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e19249},
doi = {10.1002/advs.202519249},
pmid = {41902480},
issn = {2198-3844},
support = {//This work was supported by a sponsored Research Agreement from IBA to perform preclinical research on FLASH Proton Radiotherapy (KUMC-IBA collaborative fund) and KUCC CCSG (P30 CA168524)./ ; },
abstract = {Emerging evidence shows that Proton FLASH radiotherapy can spare normal tissues while maintaining anti-tumor efficacy. However, its impact on intestinal stem cells (ISCs) and the gut microbiome remains unclear. Gut microbiome influences ISC's radiosensitivity. In a mouse model of abdominal irradiation, Proton FLASH exposure exhibited improved survival and less crypt-villus damage compared to Proton Conventional dose rate. Using scRNA-sequencing, we demonstrated that Proton FLASH exposure using pulsed pencil beam scanning spares two distinct ISC populations, Lgr5+ Crypt-based columnar cells (CBCs) and a Ly6a+, Clu+, Areg+, Anxa2+ revival stem cell (revSC) population-by modulating oxidative stress and cell cycle progression. Analysis of α and β-diversity demonstrated that Proton FLASH modulates gut microbiota composition without compromising overall species richness. Notably, Proton FLASH-irradiated mice had higher abundances of Alistipes sp. and Akkermensia sp., both known for protective effects on ISCs and the intestinal mucosa. The role of microbiome in Proton FLASH-mediated sparing effect was further confirmed by fecal microbiota transplantation, where Proton FLASH-donor microbiota demonstrated reduced lethality with protection of crypt villus morphology in recipient mice exposed to Proton Conventional dose rate. Our findings highlight the crucial role of the microbiome in the Proton FLASH-mediated sparing of the mucosal epithelium.},
}

@article {pmid41902532,
year = {2026},
author = {Belančić, A and Fajkić, A and Sener, YZ and Jelaković, A and Alić, L and Gkrinia, EMM and Verbanac, D and Jelaković, B},
title = {Gut Dysbiosis as a Shared Mechanism in Obesity and Hypertension: Exploring a Promising Therapeutic Avenue.},
journal = {Endocrinology, diabetes & metabolism},
volume = {9},
number = {3},
pages = {e70159},
doi = {10.1002/edm2.70159},
pmid = {41902532},
issn = {2398-9238},
mesh = {Humans ; *Obesity/microbiology/therapy/complications ; *Dysbiosis/therapy/complications/microbiology ; *Gastrointestinal Microbiome/physiology ; *Hypertension/microbiology/therapy/etiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Prebiotics ; },
abstract = {BACKGROUND: Obesity and hypertension are interrelated global health challenges sharing common pathophysiological mechanisms, including insulin resistance, chronic inflammation and neurohormonal dysregulation. Emerging evidence highlights the gut microbiome as a crucial mediator in this interplay, influencing intestinal barrier integrity, systemic inflammation and metabolic homeostasis.

METHODS: In this narrative review, we critically examine the interplay between obesity-induced hypertension and the gut microbiome, evaluating current evidence, therapeutic implications and future research priorities.

RESULTS: Obesity-associated gut dysbiosis disrupts the intestinal epithelial barrier, increasing translocation of bacterial products like lipopolysaccharides into circulation, promoting systemic inflammation that exacerbates insulin resistance, adipose dysfunction and hypertension. Current treatments targeting obesity, from lifestyle modification to bariatric surgery, show beneficial effects on blood pressure, but microbiome-targeted interventions are an evolving therapeutic frontier. Prebiotics, probiotics, synbiotics and faecal microbiota transplantation have demonstrated potential antihypertensive effects in preclinical and clinical studies, although findings are heterogeneous and require confirmation in larger randomised trials. Methodological challenges remain, including the need for advanced microbial sampling techniques beyond faecal analysis to fully capture disease-relevant microbiota alterations.

CONCLUSION: This review synthesises current knowledge on gut microbiome involvement in obesity-induced hypertension, evaluates microbiome-based therapeutic strategies and identifies critical research gaps to guide future investigations aimed at mitigating the dual pandemics of obesity and hypertension.},
}

Humans
*Obesity/microbiology/therapy/complications
*Dysbiosis/therapy/complications/microbiology
*Gastrointestinal Microbiome/physiology
*Hypertension/microbiology/therapy/etiology
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Animals
Prebiotics

@article {pmid41902697,
year = {2026},
author = {Tan, W and Fu, Y and Hu, W and Lin, Y and Cai, J and Huang, X and OuYang, Y and Lin, S and Ye, L},
title = {Loganic Acid Ameliorates Rheumatoid Arthritis via the Lactobacillus murinus-Inodole-3-Acetic Acid-AhR-IL-10 Axis.},
journal = {Phytotherapy research : PTR},
volume = {},
number = {},
pages = {},
doi = {10.1002/ptr.70316},
pmid = {41902697},
issn = {1099-1573},
support = {2022-SF-141//the Science and technology Plan of Qinghai Province (key Research and Development and Transformation Plan)/ ; 82274193//National Natural Science Foundation of China/ ; 82422077//National Natural Science Foundation of China/ ; 2024B1515020093//Basic and Applied Basic Research Foundation of Guangdong Province/ ; },
abstract = {Loganic acid (LA), a major iridoid glycoside from Gentiana macrophylla Pall., possesses anti-inflammatory and immunomodulatory properties, but its therapeutic potential in rheumatoid arthritis (RA) and its interaction with the gut microbiota remain poorly defined. Here, we show that LA markedly and dose-dependently attenuates disease severity in collagen-induced arthritis mice, as evidenced by reduced clinical arthritis scores, systemic inflammatory cytokines, and synovial tissue damage. LA reshaped the gut microbiota, and fecal microbiota transplantation from LA-treated donors partially reproduced its protective effects, indicating a causal contribution of the altered microbial community. In particular, LA selectively enriched OTUs annotated as Lactobacillus murinus (L. murinus) and increased levels of the microbial tryptophan metabolite indole-3-acetic acid (IAA). Both LA and IAA activated aryl hydrocarbon receptor (AhR) signaling, suppressed tumor necrosis factor-α-induced inflammatory responses in human synoviocytes, and, in vivo, enhanced IAA-AhR-interleukin-10 (IL-10) signaling in arthritic joints. Pharmacological inhibition of AhR with CH223191 substantially reversed LA's therapeutic effects, demonstrating that AhR signaling plays a critical role in its anti-arthritic activity. Collectively, these findings demonstrate that LA protects against RA through a dual mechanism: direct activation of AhR in joint tissues and indirect reinforcement of AhR signaling through an L. murinus-associated microbial IAA axis. This study highlights a gut microbiota-metabolite-AhR pathway as a key mediator of LA's anti-arthritic effects and supports LA as a promising microbiota-informed therapeutic candidate for RA.},
}

@article {pmid41902828,
year = {2026},
author = {Zhong, XS and Lopez, KM and Liu, M and Xiao, Y and Ou, R and Kochkarian, T and Powell, DW and Fujise, K and Li, Q},
title = {Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis.},
journal = {American journal of physiology. Gastrointestinal and liver physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpgi.00324.2025},
pmid = {41902828},
issn = {1522-1547},
support = {R01HL152683//HHS | National Institutes of Health (NIH)/ ; },
abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestines accompanied by profound extra-intestinal manifestations. Although IBD shows a clear clinical association with cardiovascular derangements, whether and how chronic colitis impairs heart function remains unclear. To address this gap, we investigated the impact of chronic colitis on cardiac performance and the cardiac transcriptome using two mouse models: DSS-treated and Il10[-/-] mice. Heart function was assessed by echocardiography and molecular characterization was performed using RNA-sequencing, RT-qPCR, and Western blot. Both models exhibited significant functional cardiac impairment, characterized by reduced ejection fraction and fractional shortening along with histologically evident increase in collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed a pro-fibrotic cardiac. RNA-sequencing unveiled a shared upregulation of eicosanoid-associated and inflammatory genes (Cyp2e1, Map3k6, Pck1, Cfd) across both models, alongside model-specific alterations in pathways governing cAMP and cGMP signaling, arachidonic and linoleic acid metabolism, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, while Il10[-/-] colitis yielded 105 dysregulated genes. Notably, reconstitution of a healthy balance of gut microbiota by therapeutic fecal microbiota transplantation (FMT), validated using qPCR, successfully rescued heart function and mitigated fibrosis in both models. However, Il10[-/-] mice demonstrated relatively less cardiac recovery following FMT, highlighting IL-10's cardioprotective and anti-inflammatory contribution. Collectively, these findings provide evidence that chronic colitis impairs heart function, offer novel insights into colitis-induced cardiac remodeling, and suggest that FMT mitigates cardiac dysfunction by correcting gut dysbiosis, attenuating systemic inflammation, and re-establishing homeostasis along the gut-heart axis.},
}

@article {pmid41903098,
year = {2026},
author = {Alwashmi, ASS and Khan, NU and Unar, A},
title = {Decoding Microbiota-Immune Interplay in Viral Pathogenesis: Toward Next-Generation Antiviral Therapies.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {41903098},
issn = {1867-1314},
}

@article {pmid41903138,
year = {2026},
author = {Zheng, W and Wu, C and Wang, Y and Yan, X and Han, W and Liu, X and He, C and Chen, X and Zhou, X and Zhang, L and Liu, C and Xu, J and Wang, J and Yuan, X and Song, W and Wang, X and Liang, S and Huang, J and Zhang, Y and Yang, R and Zhang, L and Qin, N and Ma, X and Xu, Q and Li, G},
title = {Mutation elevation and functional alterations in Escherichia coli are pertinent to the onset of gestational diabetes mellitus.},
journal = {Cell reports},
volume = {45},
number = {4},
pages = {117143},
doi = {10.1016/j.celrep.2026.117143},
pmid = {41903138},
issn = {2211-1247},
abstract = {In the gut microbiome, purifying selection clears deleterious mutations. However, it is unknown whether this selection pressure is modifiable or what its health implications are. Here, we studied metagenomic and metabolic changes linked to gestational diabetes mellitus (GDM), and observed an increase in Escherichia coli (E. coli) mutations during host pregnancy, linking these genetic changes to host physiology. Severe depletion of bacterial genes before GDM onset was mostly traced to E. coli despite its stable abundance-indicating that functional genetic signals outweigh taxonomic shifts. E. coli and related microbes displayed pregnancy-linked single nucleotide polymorphism elevation, enriched at GDM onset in loci encoding membrane and biofilm components. These pangenomic alterations correlated with handicapped intermicrobial interactions of E. coli and with host serum metabolic abnormalities. We propose that pregnancy relaxes purifying selection, permitting mutation elevation in certain gut bacteria. Resulting functional deficits, potentially through altered ecology and metabolism, may subsequently impact host glucose regulation.},
}

@article {pmid41903570,
year = {2026},
author = {Wang, X and Jia, Y and Wang, C and Li, D and Guo, X and Jiang, S and Zhou, Z and Gao, C and Wang, F},
title = {Decoding serotonin in endometriosis: unveiling its role in disease pathogenesis via the gut-reproductive microbiota axis.},
journal = {Human reproduction (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/humrep/deag047},
pmid = {41903570},
issn = {1460-2350},
support = {20200601011JC//Jilin Provincial Key Laboratory of Precision Infectious Diseases/ ; 3D5200117426//Key Laboratory of Health and Family Planning Commission of Jilin Province/ ; },
abstract = {STUDY QUESTION: How can the potential mechanisms and targets of endometriosis be explored through multi-omics and multi-location approaches?

SUMMARY ANSWER: This exploration of the gut-reproductive axis in patients with endometriosis found that serotonin is elevated in endometriosis and promotes disease progression through enhanced cell proliferation and inflammation.

WHAT IS KNOWN ALREADY: Endometriosis is a common inflammatory disease. Recent studies indicate that peripheral serotonin, which is regulated by the gut microbiota, can promote the progression of irritable bowel syndrome and various cancers.

STUDY DESIGN, SIZE, DURATION: This cross-sectional study enrolled 22 endometriosis patients and 22 control patients with uterine fibroids (surgical cases, October 2022-June 2023). Samples of vaginal secretions, endometrial tissue, peritoneal lavage fluid, feces, and ectopic lesions were collected from both groups. For validation, serum samples were added from 20 additional endometriosis patients and 20 healthy reproductive-age volunteers.

This study employed 16S rRNA gene sequencing to analyze the microbiota in the vagina, endometrial tissue, peritoneal fluid, and feces of patients with endometriosis and control groups, complemented by untargeted metabolomic analysis of peritoneal fluid. The results identified serotonin as a key metabolite and revealed specific bacterial species, shared between the reproductive and gastrointestinal tracts of endometriosis patients, which were significantly correlated with serotonin levels. Mendelian randomization analysis was conducted to explore the relationship between serotonin, these bacterial species, and endometriosis. Serum serotonin levels in endometriosis patients, BALB/C mouse models, and their respective controls were measured using ELISA. Immunohistochemistry and fluorescence staining were used to detect the expression of serotonin and its receptors in both ectopic and normal endometrium. The effects of serotonin on the biological behavior of various endometriosis cell models, including proliferation, migration, invasion, and apoptosis, were investigated using CCK8 assay, wound healing test, Transwell assay, apoptosis detection, ELISA, transcriptomics, and qPCR. The impact of serotonin on BALB/C mouse models was evaluated using H&E staining, flow cytometry, and ELISA.

We identified a significant enrichment of Akkermansia muciniphila (a bacterium shared by the gut and reproductive tract) in endometriosis patients, which positively correlated with peritoneal serotonin levels; Mendelian randomization analysis linked both to elevated endometriosis risk. Serotonin levels were elevated in patients' serum (using mouse models) and in ectopic endometrium, in comparison to those of controls. In vitro, serotonin boosted endometriosis cell proliferation, migration, invasion, and inflammation, with upregulated IL-17/NF-κB pathways. In mice, serotonin treatment increased lesion growth, cell proliferation, and inflammation.

LARGE SCALE DATA: N/A.

(a) The relatively limited sample size, together with potential imbalance in endometriosis ASRM stage distribution and cesarean section rates, may restrict the generalizability of our findings. In addition, due to the requirement for peritoneal lavage fluid collection, the control group could not consist of entirely healthy women, which may have resulted in a more conservative estimation of group differences. Serum sex hormone levels were not assessed; however, strict inclusion criteria and uniform surgical timing were applied to minimize hormonal confounding. Future studies incorporating cycle-phase-standardized hormone measurements may provide additional insights. (b) Dietary information was not collected in this study, despite the known influence of diet on gut microbiota composition and serotonin metabolism. (c) The direct causal relationship between Akkermansia muciniphila and elevated serotonin levels remains to be established and warrants further validation using germ-free mouse models or fecal microbiota transplantation approaches. (d) The precise mechanisms by which the gut-reproductive tract microbiota axis regulates local and systemic serotonin synthesis remain unclear and require further investigation.

Our study is the first to utilize a multi-omics approach combined with a joint analysis of the female gut-reproductive tract axis across multiple loci, revealing and validating a significant increase in serotonin levels in patients with endometriosis. This change may be regulated by the gut-reproductive microbiota axis. These findings provide new insights into the pathogenesis of endometriosis and identify potential targets for prevention and treatment.

This study was funded by the Jilin Provincial Key Laboratory of Precision Infectious Diseases (Grant No. 20200601011JC), Key Laboratory of Health and Family Planning Commission of Jilin Province (Grant No. 3D5200117426). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

TRIAL REGISTRATION NUMBER: ChiCTR2300077490.},
}

@article {pmid41903849,
year = {2026},
author = {Ekhlas, D and Verbiest, A and Stas, M and De Meyere, L and Vandermeulen, G and Tóth, J and Geboers, K and Timmermans, L and Verspecht, C and Wauters, L and Vermeersch, P and Jeppesen, PB and Verbeke, K and Joly, F and Derrien, M and Raes, J and Vanuytsel, T},
title = {Early ecological changes in intestinal microbiota with the long-acting GLP-2 analog apraglutide in short bowel syndrome.},
journal = {Clinical nutrition ESPEN},
volume = {},
number = {},
pages = {103138},
doi = {10.1016/j.clnesp.2026.103138},
pmid = {41903849},
issn = {2405-4577},
abstract = {BACKGROUND AND AIMS: Short bowel syndrome with intestinal failure (SBS-IF) is a rare, severe organ failure condition requiring long-term parenteral support. In SBS with colon-in-continuity (CiC), rapid transit and increased oxygen reshape gut and microbiota. We aimed to elucidate the effects of apraglutide, a novel long-acting glucagon-like peptide-2 (GLP-2) analogs, on the gut microbiome in SBS-IF-CiC.

METHODS: We performed a 52-week multicenter, open-label, phase 2 study in adults with SBS-IF-CiC (Leuven n = 7, Paris n = 2) receiving weekly subcutaneous apraglutide. Duodenal, distal small bowel and sigmoid colon biopsies, fecal- and plasma samples were collected over time. Analyses included mucosa-associated and fecal microbiota, fecal parameters, and fermentation metabolites. For baseline comparison, duodenal and sigmoid colonic biopsies from 20 controls (10 per region) were collected.

RESULTS: Patients exhibited an altered ecosystem characterized by reduced richness, loss of colonic anaerobes and dominance of Lactobacillus and Bifidobacterium with larger inter-subject variability, lower pH, higher moisture, and lower microbial load compared to controls. Apraglutide did not change overall diversity or stool parameters, but reduced inter-subject variability in stool and sigmoid colon. Notably, Bifidobacterium decreased in both stool and sigmoid colon, whereas Prevotella increased in stool from some patients. Still, Lactobacillus remained dominant. Specific taxa correlated with fecal butyrate, propionate, and reduced distal colonic motility, indicating microbial metabolism may support boosted adaptation.

CONCLUSIONS: This study emphasizes that SBS-IF-CiC features an immature distal gut microbiota and apraglutide promotes early ecological maturation, suggesting that combining GLP-2 analogs therapy with microbiome-targeted strategies may further enhance intestinal and ecosystem adaptation; ClinicalTrials.gov, Number NCT04964986https://www.

CLINICALTRIALS: gov/study/NCT04964986?term=NCT04964986&rank=1.},
}

@article {pmid41761093,
year = {2026},
author = {Qureshi, A and Wahid, A and Qazi, S and Shahzad, MK and Kiani, HM and Asif, MDA},
title = {DynaBiome: interpretable unsupervised learning of gut microbiome dysbiosis via temporal deep models.},
journal = {BMC bioinformatics},
volume = {27},
number = {1},
pages = {},
pmid = {41761093},
issn = {1471-2105},
abstract = {PURPOSE: Gut microbiome dysbiosis is a critical determinant for autologous fecal microbiota transplantation (Auto-FMT) eligibility, yet current classification approaches rely predominantly on supervised learning with manually annotated sequencing labels, which are often scarce. This study proposes DynaBiome, a framework designed to predict gut dysbiosis by leveraging unsupervised learning and clinical phenotypic proxies as a scalable alternative to ground-truth genomic labeling.

METHODS: Our framework employs an LSTM autoencoder architecture to capture temporal microbiome dynamics within 14-day windows. The model reconstructs normal microbiome patterns, where high reconstruction errors signal potential dysbiosis. To ensure rigorous evaluation and prevent data leakage, the dataset was partitioned via a strict patient-level split. Unsupervised anomaly signals were refined via phenotypic proxy labels (e.g., fever, neutropenia) via weak supervision, and ensemble learning methods were applied to optimize classification performance.

RESULTS: The initial LSTM autoencoder successfully flagged dysbiotic sequences but required refinement to reduce false positives. Ensemble learning significantly enhanced predictive accuracy. The stacked ensemble (with Logistic Regression meta-learner) demonstrated optimal performance with an ROC AUC of 0.8908 and a Weighted F1-score of 0.7909. This approach significantly outperformed the standard One-Class SVM baseline (ROC AUC 0.6033), confirming the superiority of deep temporal modeling over static anomaly detection. Critically, the model achieved performance levels comparable to fully supervised baselines, confirming the efficacy of the proxy-label framework.

CONCLUSION: Integrating unsupervised temporal feature extraction with stacked ensemble methods provides a viable framework for dysbiosis prediction. These results demonstrate that leveraging phenotypic via weak supervision can effectively approximate supervised baselines, thereby reducing the reliance on comprehensive metagenomic annotations for longitudinal patient monitoring.},
}

@article {pmid41894953,
year = {2026},
author = {Zhang, Y and Chen, Y and Huang, X and Gao, W and Eom, K and Dong, J and Li, L},
title = {Pterostilbene protects against doxorubicin-induced cardiotoxicity in canines via a gut microbiota-6AN-NOX2 axis.},
journal = {Pathology, research and practice},
volume = {282},
number = {},
pages = {156454},
doi = {10.1016/j.prp.2026.156454},
pmid = {41894953},
issn = {1618-0631},
abstract = {BACKGROUND: Doxorubicin (DOX) is a powerful chemotherapeutic agent, but its clinical use is restricted by cumulative and irreversible cardiotoxicity. Intestinal dysbiosis has been linked to DOX-induced cardiac injury, yet the underlying mechanisms and therapeutic targets remain elusive. This study aimed to investigate whether pterostilbene (PTE), a natural prebiotic plant extract, alleviates DOX cardiotoxicity by regulating gut microbiota and their metabolites.

RESEARCH DESIGN AND METHODS: Eighteen beagles were randomized into control, DOX (30 mg/m² weekly for 7 weeks), and PTE (50 mg/kg daily for 9 weeks) + DOX groups. Fecal microbiota transplantation (FMT) from canine donors to microbiota-depleted rats, 16S rRNA sequencing, metabolome analysis, and in vitro H9C2 cell experiments were conducted. Main outcomes included survival rate, cardiac function parameters, cardiac injury biomarkers, microbial diversity, and oxidative stress-related indicators.

RESULTS: In beagles receiving cumulative DOX (30 mg/m[2] weekly for 7 weeks), PTE cotreatment (50 mg/kg daily for 9 weeks) significantly improved survival (83.3% vs. 50.0%, n = 6/group) and attenuated myocardial injury, evidenced by reduced plasma CK and LDH activities (both p < 0.01 vs. DOX). Echocardiography revealed PTE restored LVEF and LVFS while reducing EPSS and LVIDd (p < 0.05). 16S rRNA sequencing demonstrated PTE reversed DOX induced loss of α-diversity (ACE, Shannon, Chao indices, p < 0.05) and enriched beneficial Faecalibacterium while suppressing proinflammatory Corynebacterium and Allobaculum (q<0.05). Fecal microbiota transplantation confirmed microbiota dependent cardioprotection. Metabolomics identified 6-aminonicotinamide (6AN) as a key microbial metabolite inversely correlated with cardiac damage. In H9C2 cells, 6AN (1 µM) replicated PTE's protection by restoring antioxidant enzyme activities, reducing ROS and MDA, and attenuating apoptosis (all p < 0.01), effects abolished by NOX2 overexpression.

CONCLUSIONS: PTE mitigates DOX cardiotoxicity via restructuring gut microbiota, increasing microbial metabolite 6AN, and suppressing NOX2-mediated oxidative stress. Targeting the microbiota-6AN-NOX2 axis represents a promising strategy to preserve cardiac function during anthracycline chemotherapy. These findings establish a mechanistic basis for PTE as a safe, natural adjunctive therapy in cancer patients receiving DOX.

TRIAL REGISTRATION: Not applicable.},
}

@article {pmid41895369,
year = {2026},
author = {Lin, F and Zhang, D and Liu, S and Wu, B and Wang, J and Yan, T and Jia, Y},
title = {Isoalantolactone Ameliorates Ulcerative Colitis via Gut Microbiota-Mediated Modulation of Intestinal Barrier, T Cell Homeostasis, and Metabolite Reprogramming.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178798},
doi = {10.1016/j.ejphar.2026.178798},
pmid = {41895369},
issn = {1879-0712},
abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by immune dysregulation, epithelial barrier dysfunction, and gut microbiota imbalance. This study examined the therapeutic potential of isoalantolactone (IAL), a bioactive sesquiterpene lactone naturally occurring in Inula helenium L., using a dextran sulfate sodium-induced murine colitis model. Treatment with IAL significantly mitigated weight loss, improved the disease activity index, preserved colon length, and alleviated goblet cell depletion. Mechanistically, IAL enhanced intestinal barrier integrity by upregulating tight-junction proteins zonula occludens-1, occludin, and mucin 2 and suppressing proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor-α, and IL-1β. Moreover, IAL rebalanced CD4[+]/CD8[+] T cell ratios in the colon, mesenteric lymph nodes, and spleen. Gut microbiota analysis revealed increased diversity, enrichment of beneficial taxa (Muribaculaceae, Prevotellaceae_UCG-001), and a reduced Firmicutes-to-Bacteroidetes ratio. Metabolomic profiling identified 130 differentially abundant metabolites, including increased levels of anti-inflammatory compounds (e.g., hydroferulic acid) and decreased levels of proinflammatory lipids (e.g., linoleoylcarnitine). Correlation analysis demonstrated an association between gut microbiota and faecal metabolites. In addition, faecal microbiota transplantation confirmed that IAL-modulated microbiota ameliorated colitis, with pseudo-germ-free recipients exhibiting improved barrier function and immune homeostasis. These findings highlight the importance of IAL as a novel therapeutic candidate for UC by modulating host-microbiota interactions; however, clinical validation is warranted.},
}

@article {pmid41897337,
year = {2026},
author = {Nawaz, S and Sugiura, T and Yusuf, I and Sultany, A},
title = {Gut-Heart Axis in HFpEF: The Emerging Role of Microbiome-Driven Inflammation and Endothelial Dysfunction.},
journal = {Biomolecules},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/biom16030401},
pmid = {41897337},
issn = {2218-273X},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Inflammation/microbiology/metabolism ; *Heart Failure/microbiology/physiopathology/metabolism ; Animals ; Dysbiosis/microbiology ; Stroke Volume ; *Endothelium, Vascular/physiopathology ; },
abstract = {Heart failure with preserved ejection fraction (HFpEF) represents the predominant form of heart failure, affecting over 50% of all heart failure patients with increasing prevalence in aging populations. Despite significant advances in cardiovascular medicine, HFpEF remains a complex clinical syndrome with poorly understood pathophysiology and limited treatment options. While most studies have traditionally focused on the renin-angiotensin-aldosterone system (RAAS) and other related mechanisms, emerging evidence has unveiled a critical bidirectional relationship between dysregulation of gut microbiota and HFpEF development. This phenomenon, mediated through microbiome-driven inflammation and endothelial dysfunction, introduces a novel concept and potential emerging conceptual framework in understanding HFpEF. This comprehensive review explores this novel gut-heart axis by synthesizing the latest evidence from original studies and clinical trials. We discuss novel mechanisms involving bacterial metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), bile acids, and amino acid derivatives. We also examine how gut dysbiosis may contribute to systemic inflammation through lipopolysaccharide translocation, NLRP3 inflammasome activation, and endothelial dysfunction. Furthermore, clinical trials investigating microbiome-targeted interventions, including probiotics, fecal microbiota transplantation, metabolite supplementation, and precision medicine approaches, are critically evaluated for their therapeutic potential. This review provides a framework for hypothesis generation and future research directions about therapeutic strategies targeting the gut-heart axis in HFpEF management.},
}

Humans
*Gastrointestinal Microbiome
*Inflammation/microbiology/metabolism
*Heart Failure/microbiology/physiopathology/metabolism
Animals
Dysbiosis/microbiology
Stroke Volume
*Endothelium, Vascular/physiopathology

@article {pmid41897439,
year = {2026},
author = {Xu, S and Li, X and Wu, X and Zheng, K and Yi, Y and Lin, Y and Tian, C and Zhu, Y and Tang, C and Hu, S and Zhang, S and He, Y and Chen, M and Feng, R},
title = {DUOX2-Driven Oxidative Stress Alters the Gut Redox Niche and Promotes Microbial Dysbiosis in Crohn's Disease.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {3},
pages = {},
doi = {10.3390/antiox15030292},
pmid = {41897439},
issn = {2076-3921},
support = {82341217//National Natural Science Foundation of China/ ; 82370551//National Natural Science Foundation of China/ ; 82270579//National Natural Science Foundation of China/ ; 2025YFC3408601//National Key Research and Development Program of China/ ; 2024GXNSFFA010009//Guangxi Natural Science Foundation/ ; },
abstract = {Crohn's disease (CD) is characterized by chronic intestinal inflammation accompanied by gut dysbiosis and redox imbalance. We investigated the role of dual oxidase-2 (DUOX2), a major epithelial source of reactive oxygen species (ROS), in linking oxidative stress to microbe-host crosstalk. DUOX2 expression was upregulated in human intestinal samples and was positively associated with inflammatory readouts, oxidative stress indices, and dysbiosis. Intestinal epithelial cell-specific Duox2 knockout (KO) mice exhibited reduced mucosal ROS, preserved barrier integrity, and attenuated dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Cohousing and fecal microbiota transplantation demonstrated that this protective phenotype was microbiota-dependent. Multi-omics profiling identified enrichment of Parabacteroides, particularly P. distasonis, in Duox2 KO mice, and oral supplementation with P. distasonis enhanced resistance to colitis. Mechanistically, DUOX2-derived oxidative stress constrained Parabacteroides growth, as P. distasonis displayed marked susceptibility to hydrogen peroxide, with excessive intracellular ROS accumulation and an absence of key antioxidant defenses-including peroxide reductase C (AhpC) and superoxide dismutase B (SodB)-indicating that epithelial DUOX2 shapes a hostile luminal redox niche unfavorable to these beneficial microbes. Pharmacological inhibition of DUOX2 with Compound 521 reduced oxidative stress, ameliorated colitis, and partially restored microbial balance. These findings establish a DUOX2-ROS-microbiota axis in which epithelial DUOX2 amplifies oxidative stress, remodels the gut ecosystem, and promotes inflammation, and highlights DUOX2 suppression or ROS-sensitive Parabacteroides as potential redox-centric therapeutic strategies for CD.},
}

@article {pmid41897579,
year = {2026},
author = {Ichim, C and Boicean, A and Todor, SB and Boeras, I and Anderco, P and Birlutiu, V},
title = {Clinical and MicroRNA Responses to Fecal Microbiota Transplantation in Patients with Alcohol-Related Cirrhosis: A Pilot Study.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/diagnostics16060846},
pmid = {41897579},
issn = {2075-4418},
abstract = {Background/Objectives: Alcohol-related liver cirrhosis is a systemic disorder characterized by profound immune, metabolic and gut-liver axis dysregulation. Emerging evidence highlights a bidirectional interaction between the intestinal microbiota and host microRNAs (miRNAs), positioning this axis as a potential regulator of systemic homeostasis. However, human data exploring the impact of microbiota modulation on miRNA expression in advanced liver disease remain limited. Methods: Six patients with alcohol-induced liver cirrhosis underwent fecal microbiota transplantation (FMT). Safety was assessed through clinical and paraclinical monitoring at predefined intervals. Quality of life was evaluated pre- and post-intervention using a validated liver-specific questionnaire. Fecal expression of miR-21-5p, miR-122-5p, miR-125-5p, miR-146-5p and miR-155-5p was analyzed and correlations with clinical domains, demographic variables and hepatic encephalopathy severity were explored. Results: FMT was well tolerated, with no severe adverse events reported. Preliminary improvements were observed in total clinical score (3.22 [3.06-3.57] vs. 4.25 [4.20-4.26], p = 0.001) and in several quality-of-life domains, including abdominal symptoms, fatigue, systemic manifestations, activity and emotional function (p < 0.05), while worry/concern scores remained unchanged. miR-125 and miR-146 demonstrated consistent associations with clinical status both before and after FMT, whereas miR-21 correlated mainly with age and body mass index. Notably, miR-125 and miR-146 were also associated with post-FMT hepatic encephalopathy severity, supporting their potential value as molecular correlates of clinical response in this exploratory study. Conclusions: In this pilot study, FMT appeared safe and was temporally associated with improvements in clinical parameters in alcohol-related cirrhosis, alongside dynamic changes in fecal miRNA expression. These preliminary findings support a potential microbiota-miRNA interaction and warrant validation in larger, controlled longitudinal studies.},
}

@article {pmid41898327,
year = {2026},
author = {Belosic Halle, Z and Tomasic, V and Biscanin, A and Cacic, P and Saric, I and Mustapic, S and Stojic, J and Luetic, K and Bekic, D and Paic, M and Micetic, D and Krznaric Zrnic, I and Olic, I and Razov Radas, M and Skocilic, I and Golčic, M and Rados, L and Radic, J and Prejac, J and Mikolasevic, I},
title = {Immune-Mediated Colitis Induced by Immune Checkpoint Inhibitors: Pathophysiology, Clinical Management, and the Emerging Role of Fecal Microbiota Transplantation.},
journal = {Biomedicines},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/biomedicines14030683},
pmid = {41898327},
issn = {2227-9059},
abstract = {BACKGROUND/OBJECTIVES: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, but their use is frequently accompanied by immune-related adverse events, among which immune-mediated colitis (IMC) represents one of the most common and clinically significant gastrointestinal toxicities. IMC may lead to treatment interruption, increased morbidity, and compromised quality of life. This review aims to provide a comprehensive overview of the pathophysiology, risk factors, diagnosis, management, and emerging therapeutic strategies with particular emphasis on the role of the gut microbiota and fecal microbiota transplantation (FMT).

METHODS: This review integrates current international guidelines, meta-analyses, clinical trials, and recent translational studies addressing IMC. The available evidence on immunological mechanisms, predictive biomarkers, clinical presentation, diagnostic algorithms, and treatment options was critically synthesized to outline a structured and multidisciplinary management approach.

RESULTS: IMC is driven by dysregulated immune activation, cytokine release, and alterations in gut microbiota. Incidence and severity vary according to ICI class, combination regimens, tumor type, and patient-related factors. Diagnosis requires exclusion of infectious causes, laboratory assessment, and endoscopic and histologic evaluation with CTCAE-based severity grading. Corticosteroids remain the cornerstone of first-line therapy, while infliximab and vedolizumab are effective in steroid-refractory cases. Emerging therapies, including JAK inhibitors and FMT, have shown promising results in refractory disease.

CONCLUSIONS: IMC is a complex and potentially severe complication of ICI therapy that necessitates early recognition, accurate grading, and individualized, multidisciplinary management. Severity-guided treatment, timely escalation to biologics, and careful balancing of immunosuppression with antitumor efficacy are essential for optimal outcomes. Future research should focus on biomarker validation, microbiome-targeted therapies, and prospective trials to refine therapeutic algorithms and define the optimal role and timing of FMT in clinical practice.},
}

@article {pmid41898402,
year = {2026},
author = {Antohi, AL and Gheorghiță, AD and Andronic, O and Gradisteanu Pircalabioru, G and Treteanu, AR},
title = {Across the Social Network of the Gut: Bacterial, Fungal, and Viral Determinants of Checkpoint Inhibitor Efficacy and Toxicity.},
journal = {International journal of molecular sciences},
volume = {27},
number = {6},
pages = {},
doi = {10.3390/ijms27062538},
pmid = {41898402},
issn = {1422-0067},
support = {PN-IV-P8-8.1-PRE-HE-ORG-2023-0054 - Contract no 17PHE/2023//Unitatea Executiva Pentru Finantarea Invatamantului Superior Si A Cercetarii Stiintifice Universitare/ ; grant agreement - 101087007 - eBio-hub//HORIZON-WIDERA-2022-TALENTS-01/ ; ROGEN 324809//Development of genomic research in Romania-ROGEN/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Immune Checkpoint Inhibitors/adverse effects/therapeutic use/pharmacology ; Animals ; *Neoplasms/drug therapy/immunology/microbiology ; Fungi/immunology ; Bacteria ; Dysbiosis/microbiology ; Viruses ; Mycobiome ; },
abstract = {Recent findings suggest that the gut microbiome significantly influences cancer outcomes, including responses to immune checkpoint inhibitor (ICI) treatments. Although early research focused on gut bacteria, it is now understood that the microbiome includes a bacteriome, virome, and mycobiome, all of which can modulate host immunity. Some commensal bacteria enhance anti-tumor immune responses and improve ICI efficacy, as demonstrated in both mice and patients. Fecal microbiota transplants (FMT) from patients responding to ICI have successfully reversed resistance in certain non-responders. In addition to bacteria, gut fungi and viruses are gaining attention as further factors influencing ICI effectiveness and toxicity. Recent multi-omics studies across cancer cohorts show that fungal and viral populations in the gut vary between ICI responders and non-responders. Commensal fungi may shape anti-cancer immunity by inducing inflammatory or tolerogenic pathways, while viral components can stimulate innate immune sensors that promote tumor surveillance. On the other hand, gut dysbiosis marked by expansion of pathobionts (including opportunistic fungi) and reduction in beneficial microbes is linked to serious immune-related adverse events (irAEs) such as ICI-induced colitis. This review discusses the multi-kingdom gut microbiome-bacteria, fungi, and viruses-and their interactions with the immune system in cancer therapy. We emphasize known mechanisms linking these microbes to anti-tumor immunity, overview human studies associating gut microbiome profiles with ICI outcomes and explore strategies to modulate the microbiome to enhance ICI efficacy while reducing toxicity. Understanding and utilizing the gut mycobiome and virome in conjunction with the bacteriome could pave the way for new biomarkers and therapeutic adjuvants in cancer immunotherapy.},
}

Humans
*Gastrointestinal Microbiome/drug effects/immunology
*Immune Checkpoint Inhibitors/adverse effects/therapeutic use/pharmacology
Animals
*Neoplasms/drug therapy/immunology/microbiology
Fungi/immunology
Bacteria
Dysbiosis/microbiology
Viruses
Mycobiome

@article {pmid41898651,
year = {2026},
author = {Lei, D and Zhou, C and Zheng, H and Kang, Y and Yan, Z},
title = {Fecal Microbiota Transplantation from APP/PS1 Mice Induces Th17-Related Inflammatory Parameters and Pathological Changes in the Gut-Brain Axis of Healthy C57BL/6J Mice.},
journal = {International journal of molecular sciences},
volume = {27},
number = {6},
pages = {},
doi = {10.3390/ijms27062791},
pmid = {41898651},
issn = {1422-0067},
support = {No. 2024YFHZ0334//Sichuan Provincial Science and Technology Support Program/ ; },
mesh = {Animals ; *Th17 Cells/immunology/metabolism ; *Fecal Microbiota Transplantation/adverse effects ; Mice ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; *Inflammation/pathology ; *Alzheimer Disease/microbiology/pathology/therapy ; *Brain/pathology/metabolism ; Disease Models, Animal ; Male ; Ileum/microbiology/pathology ; Mice, Transgenic ; *Brain-Gut Axis ; Amyloid beta-Protein Precursor/genetics ; },
abstract = {The gut-brain axis is increasingly implicated in Alzheimer's disease (AD) pathogenesis, but the potential correlation between AD-associated gut microbiota and central inflammation remains largely unclear. This study aimed to explore their correlative link, with a focus on changes and involvement of Th17 cell-related factors in the gut-brain axis. Healthy C57BL/6J mice were pretreated with antibiotics for 1 week to deplete the indigenous gut microbiota, followed by 2 weeks of fecal microbiota transplantation (FMT) using feces from APP/PS1 AD model mice. Hematoxylin-eosin (H&E) staining, ELISA, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), 16S rDNA sequencing, and correlation analysis were performed to evaluate ileal and central pathological changes, Th17 cell-related inflammatory mediators, ileal microbiota composition, and their potential correlations. The results demonstrated that AD-FMT significantly induced ileal inflammatory infiltration and central inflammation in recipient mice, which was accompanied by abnormal expression of Th17 cell-related indicators, elevated levels of Th17-associated inflammatory factors, upregulated RORγt mRNA expression, and perturbed ileal microbiota composition. Correlation analysis further suggested that specific ileal bacterial taxa were closely correlated with Th17 cell-related inflammatory factors. These findings suggest a potential correlation between AD-associated microbiota and central inflammation, possibly by regulating intestinal Th17 cell-related indicators and altering gut microbial composition. This study provides correlative evidence supporting the involvement of the gut-brain axis in AD-related pathogenesis, highlighting the link between gut microbiota, central inflammation and Th17-related factors.},
}

Animals
*Th17 Cells/immunology/metabolism
*Fecal Microbiota Transplantation/adverse effects
Mice
*Gastrointestinal Microbiome
Mice, Inbred C57BL
*Inflammation/pathology
*Alzheimer Disease/microbiology/pathology/therapy
*Brain/pathology/metabolism
Disease Models, Animal
Male
Ileum/microbiology/pathology
Mice, Transgenic
*Brain-Gut Axis
Amyloid beta-Protein Precursor/genetics

@article {pmid41899599,
year = {2026},
author = {Huang, J and Zhu, XH and Trotman, LC and Tsao, CK},
title = {The Role of Gut Microbiome in Prostate Cancer: Current Evidence and Emerging Opportunities.},
journal = {Cancers},
volume = {18},
number = {6},
pages = {},
doi = {10.3390/cancers18060998},
pmid = {41899599},
issn = {2072-6694},
abstract = {Prostate cancer (PCa) is one of the most common malignancies in men, and growing evidence implicates the gut microbiome as a significant, modifiable contributor to disease evolution and management. Dysbiosis influences PCa biology through effects on inflammation, immune regulation, metabolism, and hormone signaling. Microbial imbalance can promote systemic inflammation and increase intestinal permeability, activating immune signaling pathways such as NF-κB-IL-6-STAT3. In parallel, microbiome-driven metabolic effects, including IGF-1 signaling and microbial androgen synthesis or recycling, may contribute to resistance to androgen deprivation therapy (ADT). Microbial metabolites, notably short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO), exert context-dependent effects on tumor growth, treatment resistance, and progression. Conversely, beneficial microbes have been associated with improved treatment sensitivity and immune regulation. Together, these insights support the gut microbiome as a potential biomarker and emerging therapeutic target in PCa. Modulation strategies, including diet, probiotics, antibiotics, and fecal microbiota transplantation (FMT), are being explored to improve treatment response and address resistance. As mechanistic evidence continues to grow, ongoing monitoring of the gut microbiome may help inform risk stratification and treatment optimization in prostate cancer.},
}

@article {pmid41900935,
year = {2026},
author = {Santaniello, U and Mastorino, L and Pala, V and Rosset, F and Crespi, O and Quaglino, P and Ribero, S},
title = {Pharmacomicrobiomics in Psoriasis: Microbiome-Drug Interactions Across Systemic Treatments.},
journal = {Life (Basel, Switzerland)},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/life16030415},
pmid = {41900935},
issn = {2075-1729},
abstract = {Psoriasis is a chronic immune-mediated skin disease with highly variable responses to systemic therapies. Emerging evidence highlights the microbiome as a potential modulator of drug efficacy and toxicity. Gut bacteria can enzymatically metabolize drugs, such as methotrexate, altering bioavailability and therapeutic outcomes, while microbial metabolites-including short-chain fatty acids, branched-chain amino acids, and tryptophan derivatives-shape host immunity and barrier integrity, influencing drug action. Baseline microbial signatures have been linked to treatment response, potentially predicting anti-TNF or IL-17 inhibitor efficacy. Systemic therapies themselves reshape microbial communities: IL-17 blockade induces broad shifts in gut and skin microbiota, whereas cyclosporine and anti-TNF agents exert subtler effects. Small molecules such as apremilast and fumarates may reduce fungal overgrowth and influence microbial composition, whereas data on JAK/TYK2 inhibitors remain limited. Notably, current evidence exhibits a literature bias toward the gut microbiota, while the roles of the oral and skin axes remain understudied. Adjunctive microbiome-directed interventions, including probiotics and fecal microbiota transplantation, have demonstrated potential to enhance treatment outcomes by promoting anti-inflammatory taxa and restoring barrier function. Despite these promising findings, current evidence is heterogeneous, often limited by small sample sizes, short follow-up, and variable methodology. Integrating pharmacomicrobiomics data with clinical, genetic, and multi-omics profiling could enable precision medicine approaches in psoriasis, allowing therapy selection tailored to individual microbial and metabolic signatures. Future research should focus on longitudinal, multicenter studies to identify actionable microbial biomarkers, clarify mechanistic interactions between drugs, microbes, and host immunity, and evaluate microbiome-targeted adjuncts in randomized trials. Understanding the bidirectional crosstalk between systemic therapies and the microbiome may transform psoriasis management, improving efficacy, reducing adverse events, and enabling durable, personalized responses.},
}

@article {pmid41901063,
year = {2026},
author = {Nunna Sai Venkata, L and Mishra, AK and Mohanta, YK and Rustagi, S and Bahuguna, A and Tomar, A and Baek, KH and Mishra, B},
title = {The Gut Gambit: A Review of How Microbial Imbalance Fuels Metabolic Mayhem.},
journal = {Nutrients},
volume = {18},
number = {6},
pages = {},
doi = {10.3390/nu18060888},
pmid = {41901063},
issn = {2072-6643},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/metabolism ; Oxidative Stress ; *Metabolic Diseases/microbiology/metabolism ; Epigenesis, Genetic ; Probiotics ; Inflammation/microbiology ; Animals ; },
abstract = {BACKGROUND/OBJECTIVES: An imbalance in gut microbiota, known as gut dysbiosis, results in reactive oxygen species overproduction, which can cause inflammatory conditions, damage DNA, trigger immunity, and induce epigenetic modifications of crucial genes that regulate metabolic pathways. Such a condition can also weaken the resilience of the protective gut wall and elevate colon permeability, allowing toxins from the gut to reach the liver and bloodstream, contributing to oxidative damage, autoimmune diseases, and epigenetic changes linked to metabolic disorders.

METHODS: The Scopus database was exclusively searched for the literature. Relevant articles were identified using predefined keywords, including gut dysbiosis, microbiota, microbiome, oxidative stress, metabolic disorders, inflammation, and epigenetics or combinations. Gut microbiota- and diet-induced metabolic disorders, particularly obesity, insulin resistance, dyslipidemia, and hypertension, may be inherited through epigenetic pathways.

RESULTS: The evidence analyzed suggests that the gut microbiota serves as a diverse metabolic and immunological organ. Its disruption affects the production of short-chain fatty acids, bile acid metabolism, immune signaling, and the redox balance, which contributes to the development of obesity, insulin resistance, and metabolic syndrome.

CONCLUSIONS: This review highlights key epigenetic mechanisms underlying metabolic disorders and oxidative stress in the context of gut dysbiosis. Furthermore, therapeutic strategies targeting the gut microbiota, such as dietary interventions, prebiotics, probiotics, postbiotics, and fecal microbiota transplantation, hold promise for mitigating oxidative stress and inflammation associated with metabolic syndrome.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Dysbiosis/microbiology/metabolism
Oxidative Stress
*Metabolic Diseases/microbiology/metabolism
Epigenesis, Genetic
Probiotics
Inflammation/microbiology
Animals

@article {pmid41901284,
year = {2026},
author = {Bieganska, EA and Wolski, M and Zarlenga, M and Bilinski, J and Kosinski, P},
title = {Fecal Microbiota Transplantation (FMT) as a Prophylaxis of Necrotizing Enterocolitis (NEC)-Protocol for a Safety Study.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {3},
pages = {},
doi = {10.3390/ph19030437},
pmid = {41901284},
issn = {1424-8247},
support = {NA//This research is funded by statutory funds of Pediatric Surgery Clinic of the Medical University of Warsaw/ ; },
abstract = {Background/Objectives: Necrotizing enterocolitis (NEC) is an inflammatory disease with an incidence of about one in 1000 live births, much higher in premature and low birth weight newborns. Intestinal dysbiosis is an important element in the pathogenesis of NEC, and for this reason, experimental models have been used to administer fecal microbiota transplants (FMTs) for prophylaxis and treatment of NEC with very satisfactory results. The primary endpoint of the study is safety, defined as the incidence of adverse events (AEs) and serious adverse events (SAEs) occurring from the time of intervention until hospital discharge, classified according to severity and assessed for relatedness to the intervention. Methods: This prospective, single-arm, open-label clinical study will include 20 infants born between 24 0/7 and 36 6/7 weeks of gestation. FMTs will be administered twice as a deep rectal infusion via a Foley catheter. The donors of the material from which the FMT will be prepared will be women in the third trimester of pregnancy. The safety of the therapy will be assessed by comparison with a control group, i.e., 20 patients who will meet the same inclusion criteria and will not meet any of the exclusion criteria, subject to the same hospital observation but without undergoing any medical/therapeutic intervention other than the collection of biological material. Discussion: The study will provide data on the safety and initial efficacy of FMT in this group of patients, which will allow for further research into the use of this method in the prevention of infections and NEC. Ethics: The study protocol was approved by the Bioethics Committee of the Medical University of Warsaw, Warsaw, Poland (KB/52/2025). All procedures will follow the principles of the Declaration of Helsinki. The results of the study will be submitted for knowledge translation in peer-reviewed journals and presented at national and international pediatric society conferences. Clinical Trial Registration: The study is registered at ClinicalTrials.gov: ID: NCT06333405.},
}

@article {pmid41886797,
year = {2026},
author = {Misra, J and Bhargav Shreevatsa, KS and Ravi, K and Abomughaid, MM and Lakhanpal, S and Gupta, R and Jha, NK and Kumar, N},
title = {Microbiota-driven neuroimmune mechanisms in brain disorders: Microglial activation, cytokine signaling, and translational implications.},
journal = {Journal of neuroimmunology},
volume = {416},
number = {},
pages = {578913},
doi = {10.1016/j.jneuroim.2026.578913},
pmid = {41886797},
issn = {1872-8421},
abstract = {Neuroinflammation is increasingly recognized as a central driver of diverse neurological and neuropsychiatric disorders. Within this framework, the microbiota-gut-brain axis (MGBA) has emerged as a critical modulator of neuroimmune signaling rather than a broad systemic regulator. Microbial-derived metabolites and immune mediators influence central nervous system (CNS) homeostasis by shaping microglial maturation and activation, regulating cytokine signaling networks, including IL-1β, IL-6, and TNF-α and modulating inflammasome pathways, such as NLRP3. These immune mechanisms intersect with blood-brain barrier (BBB) integrity, where dysbiosis-associated inflammation and altered short-chain fatty acid (SCFA) production may compromise tight junction stability and promote peripheral immune infiltration. Through immune-glial crosstalk, microbial signals can amplify or attenuate neuroinflammatory cascades, thereby influencing vulnerability to autoimmune, neurodegenerative, and neurodevelopmental disorders. This review synthesizes current mechanistic evidence linking gut microbial perturbations to CNS immune regulation, emphasizing microglial activation, cytokine-mediated signaling, and BBB immunomodulation as core pathways. By reframing the MGBA through a neuroimmune lens, we highlight emerging therapeutic strategies targeting microbiota-driven inflammatory circuits to advance precision interventions for inflammatory brain disorders.},
}

@article {pmid41886951,
year = {2026},
author = {Zuo, G and Shen, Y and Wang, L and Gao, Y and Luo, C and Wen, J and Li, J and Huang, JA and Liu, Z and Lin, Y},
title = {Low-dose epigallocatechin gallate combined with L-theanine effectively alleviate obesity and metabolic dysfunction-associated steatotic liver disease by remodeling gut homeostasis and avoiding its hepatotoxicity.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {155},
number = {},
pages = {158078},
doi = {10.1016/j.phymed.2026.158078},
pmid = {41886951},
issn = {1618-095X},
abstract = {BACKGROUND: High-dose epigallocatechin gallate (EGCG) treats obesity and metabolic dysfunction-associated steatotic liver disease but causes hepatotoxicity, limiting its application.

OBJECTIVE: To determine whether low-dose EGCG combined with L-theanine (LTA) can reproduce the metabolic benefits of high-dose EGCG without hepatotoxicity, and to clarify the role of the gut microbiota.

METHODS: Diet-induced obese C57BL/6J mice were treated with L-EGCG (80 mg/kg/d), H-EGCG (160 mg/kg/d), LTA (80 mg/kg/d), or L-EGCG+LTA for 12 weeks. Metabolic parameters, liver function, oxidative stress, and gut barrier integrity, were evaluated. 16S rRNA sequencing and fecal microbiota transplantation (FMT) confirmed the causal role of microbiota remodeling in the observed therapeutic effects.

RESULTS: Although H-EGCG effectively reduced body weight and adiposity, it induced liver injury and gut dysbiosis with depletion of commensal butyrate producers and enrichment of polyphenol-metabolizing taxa, collectively exacerbating hepatic oxidative stress and mitochondrial injury. In contrast, L-EGCG+LTA achieved weight- and lipid-lowering effects comparable to H-EGCG while significantly attenuating hepatic oxidative stress and conferring hepatoprotective effects. Two-way ANOVA confirmed that the combined effects were predominantly additive, with both agents contributing independently. The combination additively remodeled the gut microbiota, markedly enriching beneficial taxa such as Bacteroides uniformis and Oscillospiraceae. FMT from combination-treated donors recapitulated metabolic benefits to HFD-fed recipient mice.

CONCLUSIONS: Co-administration of low-dose EGCG and L-theanine additively improves metabolic health by remodeling the gut microbiota, offering a promising strategy to enhance the safety and translational potential of EGCG-based interventions.},
}

@article {pmid41888318,
year = {2026},
author = {Huang, W and Zhang, J and Shan, J and Shen, W and Du, P and Liu, J and Guo, X and Chen, Z and Zeng, W and Lin, Q and Fan, H},
title = {Lactobacillus paragasseri LPG-9 reduces placental inflammation in intrahepatic cholestasis of pregnancy by regulating TGR5 in mice.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-09869-4},
pmid = {41888318},
issn = {2399-3642},
support = {32370139//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32300085//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Intrahepatic cholestasis of pregnancy (ICP), a liver disorder associated with adverse fetal outcomes, is characterized by elevated bile acid levels and placental inflammation by the TGR5. However, the interplay among the gut microbiome, bile acid metabolism, and ICP-associated placental inflammation remains unexplored. We aimed to investigate the role of the gut microbiota in regulating bile acid metabolism and placental inflammation, and to identify potential probiotic-based therapies for ICP in C57BL/6 mice. Immunohistochemical analysis of human placentas revealed significantly higher inflammation and decreased TGR5 expression in ICP compared with controls. In vivo and in vitro assays confirmed the anti-inflammatory effects of TGR5 activation. Using 16S rRNA sequencing and metabolomics, ICP mice exhibited a distinct gut microbiota composition and reduced abundance of bile salt hydrolase (BSH)-producing bacteria (e.g., Lactobacillus), accompanied by a significant decrease in the proportion of secondary bile acids. Transplanting fecal microbiota from ICP donors into healthy mice reproduced the disease phenotype of ICP, confirming the pathogenic role of gut microbiota dysbiosis. Supplementation with BSH-enriched Lactobacillus paragasseri LPG-9 remodeled the bile acid profile, thereby activating placental TGR5 to inhibit TLR4-NF-κB signaling and promoting hepatic bile acid excretion via BSEP.},
}

@article {pmid41889026,
year = {2026},
author = {Shi, Y and Li, H},
title = {Microecological Interventions against Antibiotic-Induced Dysbiosis and Related Resistome Expansion.},
journal = {Journal of microbiology and biotechnology},
volume = {36},
number = {},
pages = {e2601009},
doi = {10.4014/jmb.2601.01009},
pmid = {41889026},
issn = {1738-8872},
mesh = {*Dysbiosis/chemically induced/therapy/microbiology ; Humans ; *Anti-Bacterial Agents/adverse effects/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Probiotics/administration & dosage ; Prebiotics/administration & dosage ; Fecal Microbiota Transplantation ; Bacteria/drug effects/genetics/metabolism ; Drug Resistance, Bacterial ; Animals ; Synbiotics/administration & dosage ; Biofilms/drug effects ; },
abstract = {Antibiotic exposure and the emergence of antimicrobial resistance are critical global health threats, with antibiotic-induced gut dysbiosis contributing to increased mortality, prolonged illness, and significant economic burden. This review introduces the complex interplay between antibiotic exposure, gut microbiota dysbiosis, and the dissemination of antimicrobial resistance genes, which collectively undermine intestinal barrier function and promote systemic inflammation. It also explores how microbial metabolites influence resistance mechanisms through metabolic regulation, alteration of bacterial communities, antibiotic biotransformation, biofilm formation, and host-microbe interactions. Microecological interventions-including probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, dietary modifications, and emerging strategies-have the potential to restore microbial homeostasis, enhance colonization resistance to invading pathogens, and mitigate the spread of resistant pathogens. By integrating ecological and therapeutic perspectives, these approaches offer a sustainable framework for combating antibiotic resistance and improving clinical outcomes.},
}

*Dysbiosis/chemically induced/therapy/microbiology
Humans
*Anti-Bacterial Agents/adverse effects/pharmacology
*Gastrointestinal Microbiome/drug effects
Probiotics/administration & dosage
Prebiotics/administration & dosage
Fecal Microbiota Transplantation
Bacteria/drug effects/genetics/metabolism
Drug Resistance, Bacterial
Animals
Synbiotics/administration & dosage
Biofilms/drug effects

@article {pmid41889649,
year = {2026},
author = {Su, R and Ma, J and Li, J and Liu, Y and Ma, T and Wang, J and Mai, Q and Ma, Q and Wang, J and Wang, H and Yang, S and Zhang, X},
title = {Fecal microbiota transplantation ameliorates alcohol-associated liver disease through coordinated restoration of short-chain fatty acid and α-linolenic acid signaling.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1744446},
pmid = {41889649},
issn = {1664-302X},
abstract = {BACKGROUND: Alcohol-associated liver disease (ALD) is closely linked to gut microbiota dysbiosis. However, the specific microbial metabolic functions that drive the transition from microbial imbalance to hepatic inflammation and metabolic injury remain unclear, limiting the development of mechanism-based therapeutic strategies.

METHODS: This study integrated human microbiome analysis with fecal microbiota transplantation (FMT) experiments in an ALD mouse model. Multi-omics approaches, including 16S rRNA gene sequencing, untargeted metabolomics, and immunological profiling, were employed to systematically characterize the interactions among gut microbiota composition, microbial-derived metabolites, and host immune responses.

RESULTS: We observed that ALD progression was characterized by an early shift in microbial composition followed by a marked decline in microbial diversity, culminating in an ecological collapse of the gut microbiota. FMT from healthy donors significantly improved liver histopathology and serum biochemical parameters, accompanied by restoration of gut microbial diversity and key metabolic functions. Metabolomic analyses revealed enhanced short-chain fatty acid (SCFA) production and activation of α-linolenic acid (ALA)-related metabolic pathways following FMT. These metabolic improvements were associated with reduced inflammatory responses and improved immune homeostasis.

CONCLUSION: Our findings demonstrate that FMT from healthy donors ameliorates ALD by restoring critical microbial metabolic functions, particularly SCFA production and ALA-related pathways. These results highlight microbial metabolic function as a promising therapeutic target for microbiome-based interventions in ALD.},
}

@article {pmid41890300,
year = {2026},
author = {Shirotani, M and Shimizu, S and Kitamura, K and Mikawa, Y and Haruna, R and Kawai, Y and Koide, S and Mohri, I and Matsuzaki, H and Tsuchiya, KJ and Tanaka, Y and Katayama, T},
title = {Safety and efficacy of a novel fecal microbiota transplantation method using hydrogen nanobubble water without antibiotics or bowel cleansing in children with autism spectrum disorder: an open-label, single-arm study demonstrating improvements in core and comorbidity symptoms.},
journal = {Frontiers in pediatrics},
volume = {14},
number = {},
pages = {1767346},
pmid = {41890300},
issn = {2296-2360},
abstract = {BACKGROUND: Autism spectrum disorder (ASD) is rising in prevalence, but effective treatments for its core symptoms remain limited. Fecal microbiota transplantation (FMT) has shown promise; however, conventional methods often require antibiotics and bowel cleansing, raising concerns regarding safety and sustainability. We developed a novel FMT method using hydrogen nanobubble water and investigated its efficacy and safety.

METHODS: This prospective, single-arm, before-and-after comparative study enrolled 30 children aged 5-12 years with ASD, selected according to inclusion and exclusion criteria. SHIN-1, a Good Manufacturing Practice (GMP)-grade prepared fecal microbial solution from a healthy screened donor, was suspended in hydrogen nanobubble water and administered via enema. Primary outcome was the Social Responsiveness Scale-2 (SRS-2), with objectivity confirmed using Gazefinder as an eye-tracking system. Secondary outcomes included sensory profile [Short Sensory Profile (SSP)], gastrointestinal symptoms [Gastrointestinal Symptom Rating Scale [GSRS], Bristol Stool Form Scale [BSFS]] and Patient Health Questionnaire-4 items (PHQ-4). Statistical analyses employed paired t-tests or Wilcoxon signed-rank tests (α = 0.05).

RESULTS: At 30 weeks, fecal microbiota reconstitution was observed, with increases in short-chain fatty acid-producing and typically taxa abundant in developing children. SRS-2 scores decreased 29% (p < 0.001), sustained at one year. The classification is as follows; 19 severe cases improved to mild and 6 to normal. Improvements were greater in children without gastrointestinal disorders (45% vs. 24%). Social Communication and Interaction (SCI), Restricted Interests and Repetitive Behavior (RRB), and subscales improved uniformly; sensory, gastrointestinal, and emotional symptoms improved by 30%-61%. No adverse events occurred.

CONCLUSION: This novel hydrogen nanobubble water-based FMT method was safe and effective, reducing both core and peripheral symptoms of ASD and suggesting broad benefits via the gut microbiota-brain axis.Clinical Trial Registration: https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031230041.},
}

@article {pmid41890703,
year = {2026},
author = {Li, X and Liu, F and Zhu, Y and Shi, H},
title = {Gut Microbiota, Insulin Resistance, and Alzheimer's Disease: A Narrative Review of Mechanistic Links and Therapeutic Perspectives.},
journal = {International journal of general medicine},
volume = {19},
number = {},
pages = {593664},
pmid = {41890703},
issn = {1178-7074},
abstract = {Alzheimer's disease (AD) is increasingly regarded as a "neurometabolic syndrome" wherein systemic insulin resistance exacerbates cerebral glucose hypometabolism, tau hyperphosphorylation, and neuroinflammation. We hypothesize that gut microbiota dysbiosis produces metabolites that are associated with peripheral insulin sensitivity, potentially contributing to disruptions in cerebral insulin signaling and an increased risk of AD. We conducted integrated search of PubMed, Web of Science, and Scopus to synthesize evidence showing: (i) consistent taxonomic shifts in AD, highlighting reduced Firmicutes and increased Proteobacteria and Bacteroidetes, depletion of Ruminococcaceae and enrichment of Blautia and Bilophila; (ii) functional consequences of dysbiosis, leading to lower short-chain fatty acids, altered secondary bile‑acid signaling, elevated lipopolysaccharide and trimethylamine‑N‑oxide, and perturbed tryptophan catabolism; (iii) these microbial metabolites compromising gut and blood-brain barrier integrity, thereby triggering chronic inflammation, potentially modulating the PI3K‑Akt‑GSK‑3β pathway, and linking peripheral insulin resistance to cerebral dysfunction; and (iv) a translational discussion of therapeutic strategies that target both microbiota and insulin pathways, including dietary modulation, probiotics and prebiotics, fecal microbiota transplantation, intranasal insulin, metformin, and metabolite-based agents, show promise. This review uniquely integrates taxonomic, functional, and therapeutic literature to propose a mechanistic microbiota-insulin resistance-AD axis and highlights the need for longitudinal and interventional trials.},
}

@article {pmid41890764,
year = {2026},
author = {Lai, J and Wang, Y and Zeng, L and Deng, Q and Qiao, Y and Liao, J and Sun, C and Geng, Y and Wu, H and Huang, D and Zhao, X and Wu, D},
title = {Melatonin alleviates airway inflammation and anxiety-depression in asthma via gut microbiota-SCFA axis-mediated inhibition of microglial activation.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1763305},
pmid = {41890764},
issn = {1664-3224},
mesh = {Animals ; *Melatonin/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; *Asthma/drug therapy/metabolism/immunology ; *Microglia/drug effects/metabolism/immunology ; Mice ; *Fatty Acids, Volatile/metabolism ; *Depression/drug therapy/metabolism/etiology ; *Anxiety/drug therapy/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Male ; Signal Transduction ; Cell Line ; Inflammation ; },
abstract = {BACKGROUND: Asthma frequently co-occurs with anxiety and depression, yet the mechanisms underlying this lung-brain comorbidity remain elusive. The gut-lung-brain axis has emerged as a potential key mediator.

METHODS: Using an ovalbumin (OVA)-induced murine asthma model, we administered melatonin or sodium butyrate via drinking water. We assessed airway inflammation, lung function, anxiety- and depression-like behaviors, gut microbiota composition, short-chain fatty acid (SCFA) levels, and the MAPK/P65/NLRP3 signaling pathway in the hippocampus and BV2 microglial cells. Fecal microbiota transplantation (FMT) and antibiotic depletion experiments were conducted to establish causality.

RESULTS: Both melatonin and sodium butyrate significantly alleviated airway inflammation, improved lung function, and ameliorated anxiety- and depression-like behaviors in asthmatic mice. Melatonin increased gut-derived butyrate levels and restored gut microbiota balance. FMT from melatonin-treated donors replicated the therapeutic benefits, whereas antibiotic-mediated microbiota depletion abrogated the effects of melatonin. Mechanistically, both treatments inhibited the activation of the MAPK/P65/NLRP3 pathway in hippocampal microglia and LPS-stimulated BV2 cells.

CONCLUSION: Our findings demonstrate that melatonin mitigates asthma-related airway inflammation and neuropsychiatric comorbidity by modulating the gut microbiota-SCFA axis and suppressing microglial activation via the MAPK/P65/NLRP3 pathway. This study highlights a novel systemic mechanism and potential therapeutic strategy for asthma and its comorbidities.},
}

Animals
*Melatonin/pharmacology/therapeutic use
*Gastrointestinal Microbiome/drug effects
*Asthma/drug therapy/metabolism/immunology
*Microglia/drug effects/metabolism/immunology
Mice
*Fatty Acids, Volatile/metabolism
*Depression/drug therapy/metabolism/etiology
*Anxiety/drug therapy/metabolism
Disease Models, Animal
Fecal Microbiota Transplantation
Male
Signal Transduction
Cell Line
Inflammation

@article {pmid41890815,
year = {2026},
author = {Xiong, Z and Dong, X and Yuan, Y and Lu, L and Deng, X},
title = {Gut Microbiota Mitigates Chronic Itch and Cutaneous Inflammation in DNFB-Induced Atopic Dermatitis Mice.},
journal = {Journal of inflammation research},
volume = {19},
number = {},
pages = {573709},
pmid = {41890815},
issn = {1178-7031},
abstract = {BACKGROUND: Chronic itch is the most prominent symptom of atopic dermatitis (AD), which severely impacts the quality of life of patients and persists even after medication. Gut microbiota dysbiosis is considered to contribute to AD, however, the roles of gut microbiota in the modulation of chronic pruriceptive processing currently remain unclear. The present study aimed to elucidate the potential regulatory role of the gut microbiota in AD-associated chronic itch.

METHODS: In this study, the 1-fluoro-2,4-dinitrobenzene (DNFB)-induced mouse model of AD-associated chronic itch was established. Differences in gut microbiota composition between model and healthy controls were analyzed using high-throughput 16S rRNA gene sequencing. In addition, we performed oral fecal microbiota transplantation (FMT) from model mice to antibiotic cocktail-treated healthy mice and observed whether they could induce itch behavior. Furthermore, feces from healthy mice were transplanted into model mice to evaluate their effects on itch symptoms and skin inflammation.

RESULTS: The DNFB induced significantly itch behaviors and an altered gut microbiota composition. The gut microbiota from chronic itch mice through oral administration could induce itch behaviors in antibiotic cocktail-treated healthy mice. While, oral FMT from healthy mice to chronic itch mice not only significantly alleviated scratching behavior but also ameliorated skin damage and inflammation. Following FMT administration from healthy donors, remarkable alterations were observed in the metabolomic profiles of mice with DNFB-induced chronic itch.

CONCLUSION: These findings highlight the potential link between gut microbiota dysbiosis and chronic itching in AD, suggesting that targeting the gut microbiota may be a therapeutic strategy for chronic itch.},
}

@article {pmid41891399,
year = {2026},
author = {Elsheikh, M and Ibrahim, MA and Fares, S and Bhongade, M and Adhem, K and Ramirez-Morales, XI and Kaseb, AO and Petrosino, J and Hassan, MM and Jalal, PK},
title = {Influence of Gut Microbiota on Response to Immune Check Point Inhibitors in MASLD Patients With HCC: Unraveling the Connection.},
journal = {Cancer medicine},
volume = {15},
number = {4},
pages = {e71738},
doi = {10.1002/cam4.71738},
pmid = {41891399},
issn = {2045-7634},
support = {R21CA293626/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Liver Neoplasms/drug therapy/immunology/microbiology/complications ; *Carcinoma, Hepatocellular/drug therapy/immunology/microbiology/complications ; Dysbiosis/microbiology ; Drug Resistance, Neoplasm ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; },
abstract = {Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment for various cancers, including advanced hepatocellular carcinoma (HCC). However, a significant proportion of patients with HCC, particularly those with metabolic dysfunction-associated liver disease (MASLD), exhibit resistance to ICI therapy. Studies have revealed that the presence of specific gut bacteria, such as Akkermansia, Bifidobacterium, and Lachnoclostridium, is associated with improved outcomes with ICI-treated HCC patients. Conversely, the overgrowth of bacteria like Enterobacteriaceae is linked to resistance to therapy. This review investigates the role of gut microbiota in shaping immune checkpoint inhibitor responses in MASLD-related hepatocellular carcinoma, focusing on how dysbiosis may contribute to ICI resistance and exploring microbiome modulation strategies, such as fecal microbiota transplantation and probiotics, aiming to optimize therapeutic outcomes.},
}

Humans
*Gastrointestinal Microbiome/immunology/drug effects
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
*Liver Neoplasms/drug therapy/immunology/microbiology/complications
*Carcinoma, Hepatocellular/drug therapy/immunology/microbiology/complications
Dysbiosis/microbiology
Drug Resistance, Neoplasm
Fecal Microbiota Transplantation
Probiotics/therapeutic use

@article {pmid41892839,
year = {2026},
author = {Lista, AR and Ayala Mosqueda, CV and Palacios, R and García Mansilla, MJ and Rodríguez Sojo, MJ and Ho Plágaro, A and Garcia Garcia, J and Gálvez, J and Rodríguez Nogales, A and Ruiz Malagón, AJ and Rodríguez Sánchez, MJ},
title = {Modulation of Microbiome-Mitochondria Axis as a Novel Approach for Treatment of Obesity: A Scoping Review.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {1},
pages = {},
doi = {10.3390/medsci14010124},
pmid = {41892839},
issn = {2076-3271},
support = {PI18/00826, PY20-01157, PI20/01447, B-CTS-664-UGR20, PI19/01058, PI24/02089 and JDC2022-049478-I, CD23/00117, IFI21/00030//Instituto de Salud Carlos III/ ; },
mesh = {Humans ; *Obesity/therapy/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Mitochondria/metabolism ; Animals ; Probiotics/therapeutic use ; Energy Metabolism ; Fecal Microbiota Transplantation ; Prebiotics ; },
abstract = {Background: Obesity is a multifactorial, chronic disease characterised by excessive fat accumulation, low-grade inflammation, and metabolic dysfunction. Emerging evidence suggests that the gut microbiome-mitochondria axis may play a significant role in the pathophysiology of obesity, particularly in regulating energy metabolism, inflammatory responses, and mitochondrial function. However, most mechanistic insights into this axis derive from preclinical animal studies, while human evidence remains limited and largely associative. Mitochondrial dysfunction disrupts cellular energy balance, increases reactive oxygen species production, and may exacerbate gut dysbiosis, further contributing to metabolic disturbances. In addition, factors such as micronutrient deficiencies also play a relevant role in obesity development and progression. Objectives: This review aims to examine the bidirectional interactions between the gut microbiome and mitochondrial systems in obesity, with a focus on the underlying molecular mechanisms and their potential as therapeutic targets. Methods: Evidence from experimental models and clinical studies was analysed to evaluate how modulation of the microbiome-mitochondria axis through probiotics, prebiotics, dietary strategies, and faecal microbiota transplantation influences mitochondrial function, inflammation, and metabolic regulation. Results: Preclinical studies indicate that the gut microbiome modulates mitochondrial activity through the production of bioactive metabolites, including short-chain fatty acids, secondary bile acids, and tryptophan-derived compounds, which influence mitochondrial efficiency, lipid metabolism, and glucose regulation. Dysbiosis reduces these beneficial metabolites, impairing mitochondrial signalling and promoting adiposity and insulin resistance. Interventions targeting this axis have shown potential in restoring metabolic balance, improving mitochondrial function, and mitigating obesity-related complications such as hyperlipidaemia and glucose intolerance. Conclusions: Targeting the microbiome-mitochondria axis represents a promising therapeutic strategy for obesity, with the evidence based largely on preclinical findings. However, further well-designed human studies are required to clarify causality, optimise interventions, assess long-term safety and efficacy, and establish standardised clinical protocols for implementation.},
}

Humans
*Obesity/therapy/microbiology/metabolism
*Gastrointestinal Microbiome/physiology
*Mitochondria/metabolism
Animals
Probiotics/therapeutic use
Energy Metabolism
Fecal Microbiota Transplantation
Prebiotics

@article {pmid41894083,
year = {2026},
author = {Li, Y and Jiang, M and Pang, J and Ma, C and Zhang, H and Yin, F and Jia, Y and Zou, X and Zuo, T and Zhang, H},
title = {High-altitude exposure remodels the gut microbiota: health and disease.},
journal = {MedScience},
volume = {},
number = {},
pages = {},
pmid = {41894083},
issn = {3091-4981},
abstract = {With the increasing number of individuals travelling to or residing in high-altitude regions, understanding the physiological and pathological consequences of such environments has become increasingly important. High-altitude exposure poses significant challenges to human health, primarily due to hypobaric hypoxia, which triggers a cascade of responses, including energy deficiency, oxidative stress, and inflammation. One of the critical consequences is the disruption of the gut barrier, which facilitates the translocation of the gut microbiota and further exacerbates local and systemic inflammation. Notably, the gut microbiota, a dynamic environmental sensor, undergoes significant remodelling in high-altitude environments. The modified production of microbial metabolites such as bile acids influences gut homeostasis as well as glucose and lipid metabolism, and ultimately contributes to individual variability in high-altitude acclimatization. These changes have been implicated in the pathogenesis of altitude-related illnesses such as acute and chronic mountain sickness, as well as in metabolic and gastrointestinal disorders such as diabetes, obesity, irritable bowel syndrome, colorectal cancer, cholelithiasis, and osteoporosis. Preliminary explorations have demonstrated the therapeutic potential of microbiome-based interventions such as faecal microbiota transplantation in acute and chronic mountain sickness. Further research into gut microbiota modulation may provide applicable options for promoting high-altitude acclimatization and preventing high-altitude illness.},
}

@article {pmid41880553,
year = {2026},
author = {Liao, Y and Jiang, R and Zhang, H and Zhang, W},
title = {The dual roles of microorganisms in inflammatory diseases: initiators and regulators.},
journal = {Critical reviews in clinical laboratory sciences},
volume = {},
number = {},
pages = {1-33},
doi = {10.1080/10408363.2026.2637106},
pmid = {41880553},
issn = {1549-781X},
abstract = {Research on the microbiome is reshaping the conceptual foundations of inflammatory diseases. As a dynamic component of the host ecosystem, microbial communities collectively influence inflammatory responses and homeostatic balance through their metabolites, structural signals, and interactions with immune pathways. Dysbiosis can amplify immune activation and metabolic disturbances, leading to persistent inflammation, whereas specific commensal taxa and their metabolites possess the capacity to suppress excessive immune responses and restore homeostasis. This bidirectional regulatory capacity positions the microbiome as a central node that both drives and modulates inflammatory networks. Multi-omics investigations have delineated the systemic architecture of microbe-host interactions, revealing cross-system axes such as the gut-brain, gut-liver, and skin-gut pathways that constitute a signaling framework integrating inflammation and immunity, thereby reshaping our understanding of disease pathogenesis. Within this framework, inflammation is redefined as an adaptive strategy for maintaining systemic stability rather than merely a singular pathological reaction. Therapeutic approaches including fecal microbiota transplantation (FMT), engineered microbial strains, and interventions targeting metabolic signaling are propelling microecological medicine into an era of precision modulation. As systems biology converges with spatial omics, research on the microbiome is shifting from descriptive pathology toward mechanistic control, establishing it as a critical nexus linking immunity, metabolism, and disease evolution. This transformation heralds a paradigm shift in medicine from merely "suppressing inflammation" to actively "reconstructing ecological order."},
}

@article {pmid41883804,
year = {2026},
author = {Han, Y and Wang, Z and Xie, J and Yang, G and Su, M and Wang, S and Yang, M and Yu, H and Li, M and Wang, L and Zhang, Y and Hou, B},
title = {Host-gut microbiota interactions in health and disease: mechanisms and intervention strategies.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1785607},
pmid = {41883804},
issn = {1664-302X},
abstract = {The mammalian gut microbiota is a complex and dynamic "microbial organ" that interacts with its host. The gut microbiota contains a vast gene pool and metabolic capacity, producing key metabolites such as short-chain fatty acids (SCFAs), bile acids, vitamins, and other compounds. These metabolites regulate core physiological functions like energy metabolism, immune homeostasis, and neural behavior via the gut-brain axis (GBA), immune signaling networks, and other pathways. This review explores the bidirectional regulatory role of the gut microbiota. The gut microbiota influences the host's metabolism and immune functions through its metabolites and structural components, while the host's physiological state, internal environment, and lifestyle can alter the microbiota's composition and function, creating a complex feedback network. Furthermore, the main mechanisms of dysbiosis in diseases are also explored. Dysregulation of the gut microbiota can damage the intestinal mucosal barrier, induce chronic inflammation, disrupt metabolic and immune signaling, and contribute to diseases such as type 2 diabetes, non-alcoholic fatty liver disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative disorders. Microbiota-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), can be promising in disease management, but their clinical applications face challenges, including individual genetic backgrounds, lifestyles, and environmental factors, as well as difficulties in achieving long-term colonization of specific strains. Future research needs to uncover precise causal mechanisms in host-microbe interactions, as well as develop individualized microbiota intervention strategies to provide new theoretical bases and practical tools for the prevention, diagnosis, and treatment of major diseases.},
}

@article {pmid41884305,
year = {2023},
author = {Ito, K and Haraguchi, A and Sato, S and Sekiguchi, M and Sasaki, H and Ryan, C and Lyu, Y and Shibata, S},
title = {Feeding with resistant maltodextrin suppresses excessive calorie intake in a high-fat diet, mediated by changes in mouse gut microbiota composition, appetite-related gut hormone secretion, and neuropeptide transcriptional levels.},
journal = {Frontiers in microbiomes},
volume = {2},
number = {},
pages = {1149808},
pmid = {41884305},
issn = {2813-4338},
abstract = {Consuming resistant maltodextrin (RMD) decreases food intake and increase appetite-related gut hormones, but the underlying mechanisms have remained unknown. Therefore, we aimed to elucidate the mechanisms underlying the effects of RMD feeding on food intake (appetite) using Institute of Cancer Research male mice fed with a high-fat diet (HFD-cellulose group) or HFD in which cellulose was replaced with RMD (HFD-RMD group). Feeding mice with an HFD-RMD for approximately 8 weeks inhibited excessive calorie intake and altered the gut microbiota composition. Excessive calorie intake was inhibited for several days in mice fed only with an HFD-cellulose and transplanted with fecal microbiota from the HFD-RMD group (FMT-HFD-RMD group). Moreover, in the HFD-RMD and FMT-HFD-RMD groups, serum active glucagon-like peptide (GLP)-1 and peptide tyrosine tyrosine (PYY) levels were significantly higher, and appetite-related neuropeptide gene transcription in the hypothalamus were significantly altered, compared with the HFD-cellulose and FMT-HFD-cellulose groups. These results suggested that the long-term RMD intake changed the gut microbiota composition, increased the GLP-1 and PYY secretion, and altered the appetite-related neuropeptide gene transcription in the hypothalamus, leading to suppressed excessive calorie intake in an HFD.},
}

@article {pmid41876026,
year = {2026},
author = {Celis, A and Quera, R and Núñez, P and von Muhlenbrock, C and Espinoza, R and Concha, A and Mendoza, C and Marcet, F and Araya, D and Fuentes, J and Riesco, F and Correa, P},
title = {Long-term effectiveness and safety of colonoscopy-guided Fecal Microbiota Transplantation in recurrent Clostridiodes difficile infection: a prospective case series.},
journal = {Gastroenterologia y hepatologia},
volume = {},
number = {},
pages = {502719},
doi = {10.1016/j.gastrohep.2026.502719},
pmid = {41876026},
issn = {0210-5705},
}

@article {pmid41877779,
year = {2026},
author = {Sun, S and Long, F and Su, B and Chen, J and Luo, Y and Zhong, Y and Zhang, G},
title = {The gut microbiome in colorectal anastomotic leakage: from mechanisms to precision.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1781458},
pmid = {41877779},
issn = {2296-858X},
abstract = {Anastomotic leakage after curative colorectal cancer resection remains a frequent and severe complication that increases short-term mortality, worsens long-term oncologic outcomes, and places substantial burdens on individuals and health systems despite advances in surgical technique and perioperative care. Emerging evidence redefines anastomotic failure as not only a technical event but also a biologically driven process in which the gut microbiome regulates inflammation, epithelial repair, and barrier integrity at the healing interface. This review summarizes current data on the dual role of the intestinal microbiome in promoting physiological anastomotic healing and driving pathological leakage when perioperative stressors cause dysbiosis. Mechanistic sections describe how a diverse, metabolically active community supports collagen stability through short-chain fatty acid production, immune regulation, and maintenance of mucus and tight junction architecture. In contrast, the enrichment of microbial groups such as Enterococcus faecalis, Fusobacterium nucleatum, and Alistipes onderdonkii together with fungal and viral shifts, has been associated with extracellular matrix degradation and excessive inflammation. Furthermore, the review examines microbiome-related biomarkers for risk assessment, including DNA-based microbial signatures, metabolite profiles, and host immune markers. It also discusses how integrated multi-omics models combined with machine learning may outperform traditional clinical scores for preoperative and early postoperative prediction. Finally, the article critically evaluates perioperative microbiome-directed strategies ranging from dietary prehabilitation and microbial supplementation to selective decontamination and fecal microbiota transplantation, highlighting promising signals, variability of effect, safety considerations, and key methodological limitations that currently prevent routine implementation. In summary, this review addresses three interconnected domains-mechanisms of microbiome-driven anastomotic failure, microbiome-derived biomarkers for risk stratification, and perioperative intervention strategies-underscoring that AL is best understood as a host-microbiome interaction rather than a purely technical failure. This framing offers surgeons and perioperative teams a biologically rational basis for prevention, yet clinical translation will require causal validation, standardized intervention algorithms, and interpretable computational tools embedded into real-world perioperative practice.},
}

@article {pmid41878444,
year = {2026},
author = {Chen, Y and Wang, Z and Zeng, Y and Xie, X and Liu, L and Qian, Y},
title = {Research progress on the role of gut microbiota dysbiosis in the pathogenesis of immune-mediated liver diseases.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1708826},
pmid = {41878444},
issn = {1664-3224},
mesh = {Humans ; *Dysbiosis/immunology/therapy/microbiology/complications ; *Gastrointestinal Microbiome/immunology ; Animals ; *Liver Diseases/immunology/microbiology/etiology/therapy ; Hepatitis, Autoimmune/microbiology/immunology ; Fecal Microbiota Transplantation ; },
abstract = {Gut microbiota dysbiosis plays a significant role in the pathogenesis of immune-mediated liver diseases (IMLDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), through multiple gut-liver axis mechanisms. Microbial metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids regulate hepatic immune homeostasis by activating G protein-coupled receptors (GPRs) and the farnesoid X receptor (FXR). Concurrently, disruption of the intestinal barrier integrity allows endotoxins (e.g., lipopolysaccharide) to activate hepatic macrophages via the TLR4/NF-κB pathway, triggering a pro-inflammatory cytokine cascade. Studies indicate an enrichment of Veillonella in AIH patients, while PBC patients display elevated Enterobacteriaceae and reduced Oscillospira spp. PSC is characterized by Klebsiella pneumoniae translocation and Candida albicans toxin-mediated injury. Therapeutic strategies such as fecal microbiota transplantation (FMT), probiotics, prebiotics, and bacteriophages therapy have shown efficacy in clinical settings, underscoring the potential of targeting the gut microbiota for managing IMLDs. Future research should integrate immune cell regulation by gut-derived factors and develop precision therapies based on the gut-liver axis.},
}

Humans
*Dysbiosis/immunology/therapy/microbiology/complications
*Gastrointestinal Microbiome/immunology
Animals
*Liver Diseases/immunology/microbiology/etiology/therapy
Hepatitis, Autoimmune/microbiology/immunology
Fecal Microbiota Transplantation

@article {pmid41878631,
year = {2026},
author = {MacDonald, KV and Pai, N and Burow, C and deBruyn, JC and Huynh, HQ and Otley, A and Rozario, S and Marshall, DA},
title = {Balancing safety and effectiveness: parent preferences for fecal microbiota transplant and established therapies in pediatric inflammatory bowel disease-results of a multicenter Canadian study.},
journal = {Crohn's & colitis 360},
volume = {8},
number = {1},
pages = {otag016},
pmid = {41878631},
issn = {2631-827X},
abstract = {BACKGROUND AND AIMS: Treatment decision-making in pediatric inflammatory bowel disease (IBD) is complex, with many existing and emerging options. However, little is known about parent preferences for these therapies. This multi-center Canadian study provides the first quantitative data on parent preferences for pediatric IBD treatments and explores characteristics associated with differing preferences.

METHODS: We conducted a cross-sectional survey including a discrete choice experiment (DCE) with Canadian parents (n = 159) of children diagnosed with UC/IBD-U, recruited from four pediatric IBD clinics. The DCE assessed preferences across four treatment attributes: chance of clinical remission, severity and chance of known side effects, severity of rare unknown side effects, and mode of treatment delivery. Latent class modeling was used to explore preference heterogeneity.

RESULTS: Parents prioritized safety, particularly the risk of rare unknown side effects, followed by likelihood of remission. Latent class analysis identified two distinct groups: one most concerned about rare unknown side effects, and another prioritizing treatment effectiveness. Thirty-eight percent of parents were open to fecal microbiota transplant (FMT), an emerging therapy that uses donor stool to help restore gut microbiome health. Younger parents and those with children experiencing more severe disease and on multiple medications were more likely to accept FMT. Across the cohort, many parents were willing to trade off less desirable delivery modes or increased risk in exchange for better treatment outcomes.

CONCLUSIONS: Parents value both safety and effectiveness in IBD treatment decisions. Recognizing these preferences may support shared decision-making, particularly when discussing novel therapies like FMT.},
}

@article {pmid41878811,
year = {2026},
author = {Chen, Y and Li, B and Lin, Y and Sha, W and Shi, C and Wang, M and Wang, S and Wang, J and Ma, Y and Wu, M and Fan, Z and Chen, Y and Zhou, Y and Fu, D and Li, J and Zheng, Y and Hu, L},
title = {Hypertension-Associated Acetate Deficiency Enhances Platelet Activation and Thrombosis Via Olfr78.},
journal = {Circulation research},
volume = {},
number = {},
pages = {},
doi = {10.1161/CIRCRESAHA.125.327498},
pmid = {41878811},
issn = {1524-4571},
abstract = {BACKGROUND: Arterial thrombotic events constitute the leading cause of mortality in hypertension. Gut dysbiosis induces endothelial dysfunction and systemic inflammation, contributing to hypertension and its associated cardiovascular complications. Whether these dysbiotic microbiota metabolites in hypertension directly regulate platelet hyperactivation and thrombosis remains unclear.

METHODS: Fecal microbiota transplantation, 16S rRNA sequencing, and untargeted metabolomics were performed using samples from patients with hypertension. In vivo FeCl3-induced mesenteric arteriole thrombosis model, ex vivo microfluidic whole-blood perfusion assay, and in vitro platelet functional studies defined the functional effects of acetate on platelet activation. Moreover, platelet-specific Olfr78 (olfactory receptor 78)-deficient mice were employed to explore the underlying mechanisms of acetate on platelet activation.

RESULTS: Transplantation with fecal microbiota from patients with hypertension enhanced in vivo FeCl3-injured mesenteric arteriole thrombosis and ex vivo whole blood thrombus formation compared with fecal microbiota from healthy normotensive subjects. Untargeted metabolomics revealed that gut microbiota-derived acetate was decreased in patients with hypertension, and plasma acetate concentration negatively correlated with integrin αIIbβ3 activation and P-selectin exposure. Acetate demonstrated superior antiplatelet efficacy against ADP-induced aggregation, dense-granule secretion, α-granule secretion, and integrin αIIbβ3 activation than collagen or thrombin-induced platelet activation. Mechanistic studies using platelet-specific Olfr78[-/-] mice revealed that acetate bound to and activated Olfr78, a receptor not previously reported to be expressed in platelets, to elevate cAMP level and activate PKA, thereby increasing p-VASP and decreasing Ca[2+] mobilization as well as inactivating RhoA/ROCK2/MLC (myosin light chain) signaling to inhibit platelet activation. A high-fiber diet upregulated acetate/Olfr78 signaling in platelets to suppress microvascular thrombosis and protect against myocardial injury during myocardial infarction in mice.

CONCLUSIONS: Acetate is a negative regulator of platelet hyperreactivity and thrombus formation via the Olfr78 receptor, and acetate deficiency contributes to platelet hyperreactivity in hypertension. Lifestyle modifications, particularly high-fiber dietary intervention and acetate supplementation, exhibit potent antithrombotic effects in hypertension.},
}

@article {pmid41880488,
year = {2026},
author = {Kim, SG and Ott, R and Bretin, A and Abo, H and Wang, Y and Wang, Y and Winer, S and Winer, DA and Reddivari, L and Heaver, SL and Ley, RE and Pellizzon, M and Ngo, VL and Gewirtz, AT},
title = {Wheat fiber mitigates colitis via non-SCFA microbial metabolite-trained intestinal macrophages.},
journal = {Science advances},
volume = {12},
number = {13},
pages = {eaec5757},
doi = {10.1126/sciadv.aec5757},
pmid = {41880488},
issn = {2375-2548},
mesh = {Animals ; *Dietary Fiber/pharmacology/administration & dosage ; *Macrophages/metabolism/drug effects ; *Colitis/metabolism/pathology/microbiology/prevention & control/etiology ; *Triticum/chemistry ; Mice ; *Gastrointestinal Microbiome ; *Fatty Acids, Volatile/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Germ-Free Life ; Male ; Feces/microbiology ; },
abstract = {The advent of highly refined wheat products has reduced fiber consumption, which is associated with increased risk for inflammatory bowel disease (IBD). We found that enriching diets with wheat fiber (WF) protected mice against colitis, especially relative to a low-fiber diet, as assessed by clinical, histopathologic, morphologic, and immunologic parameters. WF's protection against colitis was independent of short-chain fatty acids (SCFAs) yet associated with preservation of microbiota diversity, including maintenance of Bacteroides thetaiotaomicron (B. theta), which was necessary and sufficient for WF's colitis protection. B. theta's presence in gnotobiotic mice resulted in WF-induced fecal metabolites that reprogrammed macrophages toward an M2-like phenotype. Metabolic and phenotypic reprogramming of macrophages ex vivo via WF-induced metabolites, followed by their transplantation into mice, recapitulated WF's protection against colitis. Thus, microbiota-mediated metabolism of WF promotes macrophages that reduce proneness to intestinal inflammation, suggesting a mechanism by which WF consumption may curb development of IBD.},
}

Animals
*Dietary Fiber/pharmacology/administration & dosage
*Macrophages/metabolism/drug effects
*Colitis/metabolism/pathology/microbiology/prevention & control/etiology
*Triticum/chemistry
Mice
*Gastrointestinal Microbiome
*Fatty Acids, Volatile/metabolism
Mice, Inbred C57BL
Disease Models, Animal
Germ-Free Life
Male
Feces/microbiology

@article {pmid41871943,
year = {2026},
author = {Awoniyi, M and El Hag, M and Hernandez, J and Yang, Q and Evans, N and Nemet, I and Ngo, B and Coskuner, D and Zhou, J and Farmer, M and Su, L and Zhou, H and Roach, J and Stappenbeck, T and Sartor, RB},
title = {Dysbiotic microbiota trigger colitis-associated colorectal cancer and imprint a distinctive bile acid profile in a PSC-IBD model.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2025-336675},
pmid = {41871943},
issn = {1468-3288},
abstract = {BACKGROUND: Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction.

OBJECTIVE: To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss.

DESIGN: Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)[-/-] × interleukin (IL)-10[-/-] double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling.

RESULTS: PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10[-/-] donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2[-/-] donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity.

CONCLUSION: PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction.},
}

@article {pmid41872963,
year = {2026},
author = {Kim, B and Kim, HN and Cheong, HS and Jeong, S and Kim, J and Park, DI and Joo, EJ},
title = {Fecal microbiota from hepatitis B-infected individuals alters triglyceride metabolism and microbial pathways in mice.},
journal = {Gut pathogens},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13099-026-00825-5},
pmid = {41872963},
issn = {1757-4749},
support = {RS-2023-KH135855//Korea Health Industry Development Institute/Republic of Korea ; NRF-2021R1A2C4002454//National Research Foundation of Korea/ ; },
}

@article {pmid41873114,
year = {2026},
author = {Wang, D and Cui, R and You, C and Zheng, W and Wang, L and Yang, Y and Yu, H and Cui, B},
title = {Relationship Between Gut Microbiota and Cancer Neuro-Immunity.},
journal = {Microbial biotechnology},
volume = {19},
number = {3},
pages = {e70336},
doi = {10.1111/1751-7915.70336},
pmid = {41873114},
issn = {1751-7915},
support = {K2023011//Medical research key project of Jiangsu Commission of Health/ ; },
mesh = {*Gastrointestinal Microbiome/immunology ; Humans ; *Neoplasms/immunology/therapy/microbiology/pathology ; Animals ; Immunotherapy ; Probiotics ; Tumor Microenvironment/immunology ; *Neuroimmunomodulation ; Prebiotics/administration & dosage ; },
abstract = {The nervous system and the immune system are integral components of the tumour microenvironment, and neuroimmune mechanisms play critical roles in tumour metastasis, immune evasion and metabolic reprogramming. However, the relationship between the gut microbiota and cancer neuro-immunity remains poorly understood. This knowledge gap hampers our understanding of how these systems contribute to tumour progression and therapeutic resistance. This article systematically explores the interactions among the gut microbiota, the nervous system and the immune system in the regulation of tumour progression, with a particular focus on elucidating the pathways by which the gut microbiota and its metabolites modulate tumour phenotypes via neuroimmune mechanisms, and summarises the regulatory mechanisms through which cancer neuro-immunity shapes gut microbiota composition. Additionally, this article summarises the interplay between immunotherapy and cancer neuro-immunity, and explores the potential of microbiota-based interventions, such as faecal microbiota transplantation, probiotics, prebiotics and synbiotics, to enhance the efficacy of immunotherapy through neuroimmune mechanisms.},
}

*Gastrointestinal Microbiome/immunology
Humans
*Neoplasms/immunology/therapy/microbiology/pathology
Animals
Immunotherapy
Probiotics
Tumor Microenvironment/immunology
*Neuroimmunomodulation
Prebiotics/administration & dosage

@article {pmid41873461,
year = {2026},
author = {Mattavelli, E and Da Prat, V and Corallo, S and Tartara, A and Figini, S and De Simeis, F and Marino, S and Uggè, A and Caccialanza, R and Pedrazzoli, P and Lasagna, A},
title = {Harnessing the gut microbiota in extra-intestinal cancers: from causal evidence to immunotherapy strategies.},
journal = {Immunotherapy},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/1750743X.2026.2648431},
pmid = {41873461},
issn = {1750-7448},
abstract = {The gut microbiota (GM) has emerged as a key modulator of cancer development and therapeutic response beyond the gastrointestinal tract. In extra-intestinal cancers, GM composition influences oncogenesis, with specific microbial taxa and their metabolites linked to either increased or decreased cancer risk, as highlighted by Mendelian Randomization studies. Beyond cancer initiation, GM plays a critical role in shaping the efficacy and toxicity of anticancer therapies, particularly immunotherapy. We searched PubMed and ClinicalTrials.gov using the terms"gut microbiota," "immune checkpoint inhibitors," "faecal microbiota transplantation," "solid tumor" in oncology patients. Evidence indicates that SCFA-producing bacteria, Akkermansia muciniphila, and members of Lachnospiraceae and Ruminococcaceae families enhance responses to immune checkpoint inhibitors (ICIs), whereas dysbiosis and immunosuppressive bacteria are associated with poor outcomes and immune-related adverse events. Therapeutic modulation of the GM through probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions shows promise in optimizing immunotherapy efficacy, yet standardized clinical protocols remain lacking. Integrating GM profiling with multi-omics and artificial intelligence approaches offers a path toward personalized microbiota-targeted interventions to improve patient outcomes. This review critically summarizes current evidence linking GM to cancer immunotherapy, discusses mechanistic insights, and outlines future perspectives for translating microbiota modulation into clinical practice.},
}

@article {pmid41873680,
year = {2026},
author = {Zhang, S and Li, P and Dai, M and Wu, X and Lu, C and Lu, G and Ren, Q and Wang, X and Si, Y and Chang, L and Tang, S and Wu, J and Yuan, L and Lyu, L and Wang, H and He, F and Ding, J and Huang, G and Pan, X and Mei, Y and Li, L and Hu, S and Huang, X and Cui, B and Zhang, F and Wen, Q},
title = {Washed Microbiota Transplantation as a Rescue Therapy for Refractory Unidentified Pathogen Intestinal Infections: Findings From a National Multi-Centre, Real-World Study.},
journal = {Microbial biotechnology},
volume = {19},
number = {3},
pages = {e70335},
doi = {10.1111/1751-7915.70335},
pmid = {41873680},
issn = {1751-7915},
support = {82400648//National Natural Science Foundation of China/ ; 82170563//National Natural Science Foundation of China/ ; 2021YFA0717004//National Key Research and Development Program of China/ ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; Retrospective Studies ; *Fecal Microbiota Transplantation/methods/adverse effects ; Aged ; Treatment Outcome ; China ; Adult ; *Intestinal Diseases/therapy/microbiology ; Anti-Bacterial Agents/therapeutic use ; Prospective Studies ; Aged, 80 and over ; Diarrhea/therapy ; },
abstract = {Unidentified pathogen intestinal infections (UPIIs) represent a severe clinical dilemma, characterised by clear signs of intestinal infection yet no identifiable causative pathogen, often leading to prolonged, antibiotic-refractory illness. A nationwide retrospective study based on the prospective cohorts from September 2015 to February 2025 was conducted in China to evaluate washed microbiota transplantation (WMT) on this challenging condition. Patients diagnosed with UPIIs and then underwent WMT were included. The primary outcome was the clinical response rate one month post-WMT. Finally, among the 81 included patients, 71.6% were bedridden, 46.9% required ICU admission and 51.9% developed multiple organ dysfunction syndrome. Diarrhoea was the primary symptom, and over half received ≥ 3 empirical antibiotics. Despite the challenges, WMT achieved a one-month clinical response rate of 63.0% and a cure rate of 43.2%. Multivariate analysis identified several baseline risk factors affecting WMT efficacy, including adverse events (AEs) related to WMT (β = 1.545, p = 0.026, OR = 4.690, 95% CI 1.208-18.206), total abdominal symptom scores (TASS) before WMT (β = 0.292, p = 0.047, OR = 1.340, 95% CI 1.004-1.788) and WHO performance status score ≥ 4 (β = 1.583, p = 0.031, OR = 4.867, 95% CI 1.160-20.423). The overall AEs rate was only 8.3% (18/216). A nomogram based on logistic regression [akaike information criterion (AIC) = 93.75] was developed to predict the clinical non-response at one month after WMT. The favourable clinical outcomes observed in this study provide cohort-based evidence on using WMT for treating refractory UPIIs. These findings implied that if WMT is available, earlier WMT may be beneficial for UPIIs.},
}

Humans
Male
Female
Middle Aged
Retrospective Studies
*Fecal Microbiota Transplantation/methods/adverse effects
Aged
Treatment Outcome
China
Adult
*Intestinal Diseases/therapy/microbiology
Anti-Bacterial Agents/therapeutic use
Prospective Studies
Aged, 80 and over
Diarrhea/therapy

@article {pmid41874370,
year = {2026},
author = {Liu, C and Dan, L and Wang, X and Chen, L and Yuan, X},
title = {Gut microbiota impact on lung diseases: a mini review of clinical evidence.},
journal = {Infection and immunity},
volume = {},
number = {},
pages = {e0043025},
doi = {10.1128/iai.00430-25},
pmid = {41874370},
issn = {1098-5522},
abstract = {The gut-lung axis represents a bidirectional communication network through which the gut microbiota (GM) influences respiratory health. This mini-review synthesizes clinical evidence on the role of the GM in lung diseases. We focused exclusively on human clinical trials, randomized controlled trials, meta-analyses, and systematic reviews, sourced from major databases after duplicate removal. The evidence indicates that GM dysbiosis is a significant risk factor for the susceptibility and severity of various respiratory conditions, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and infections, such as COVID-19 and pneumonia. Specific microbial signatures and metabolic profiles, particularly involving short-chain fatty acids (SCFAs), are associated with disease states and outcomes. Interventions like probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) show promise in modulating the GM and improving clinical parameters, though their efficacy can be inconsistent and influenced by confounding factors. In conclusion, the GM is a promising therapeutic target for lung diseases. However, future research must prioritize large-scale, longitudinal clinical trials and deeper mechanistic investigations to establish causality and develop effective, personalized microbiome-based therapies.},
}

@article {pmid41874416,
year = {2026},
author = {Koseli, E and Tyc, KM and Buzzi, B and Akbarali, HI and Damaj, MI},
title = {The Role of the Gut Microbiome in Nicotine Withdrawal and Dependence.},
journal = {Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco},
volume = {},
number = {},
pages = {},
doi = {10.1093/ntr/ntag057},
pmid = {41874416},
issn = {1469-994X},
abstract = {INTRODUCTION: Smoking is considered a global pandemic with more than 1.3 billion people being active smokers. Increasing evidence suggests that nicotine exposure can lead to changes in the gut microbiome, increases in permeability, and impaired mucosal immune responses in the gastrointestinal tract. However, the literature on behavioral aspects of nicotine-microbiome interaction, such as dependence and withdrawal, is limited. In this study, we used homologous fecal material transplants (FMT) to modify the gut microbiome and its impact on the intensity of nicotine withdrawal in mice.

METHODS: We used osmotic minipumps as an application of chronic nicotine for 15 days and orally gavaged FMT 2x a day to the mice. We assessed the nicotine withdrawal by measuring the number of somatic signs and anxiety-like behaviors at 24 h and 1 week after the mini pump removal. Fecal samples were also collected points to identify the gut microbiome changes.

RESULTS: Fecal transplants reduced the number of somatic signs and anxiety-like behaviors in nicotine-treated mice up to a week after the removal of minipumps. The shotgun metagenomic results of the fecal samples from 24 h after minipumps removal time point show altered gut microbiome with a significant shift in the species composition between the nicotine treated and its homologous FMT treatment.

CONCLUSIONS: Our results indicate that under our experimental conditions fecal transplant can reduce the severity of nicotine withdrawal. This suggests that interactions along the gut-brain axis are important for the development of nicotine dependence and might help lower the risk of cancer and other serious health problems in humans.},
}

@article {pmid41875216,
year = {2026},
author = {Castillo-Moral, Á and Toda-Ferran, C and Bulló, M and Teichenné, J and Escoté, X},
title = {Nutraceuticals and the Microbiota-Gut-Brain Axis: A Pathway for Preventing Cognitive Decline.},
journal = {Nutrition reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/nutrit/nuag017},
pmid = {41875216},
issn = {1753-4887},
support = {//Vicente Lopez Program (Eurecat)/ ; //Autonomous Government of Catalonia/ ; 2021 SGR 00213//Departament de Recerca i Universitats de la Generalitat de Catalunya to the Nutrition and Metabolic Health Research Group/ ; 2021 SGR 01556//Precision Nutrition, Wellness and Prevention of Metabolic Diseases/ ; },
abstract = {With the global rise in aging populations, cognitive impairment and neurodegenerative diseases, such as Alzheimer's disease (AD), present a growing public health issue. Current pharmacological treatments primarily target symptoms rather than underlying causes, necessitating the exploration of alternative preventive strategies. Nutraceuticals have emerged as promising candidates for neuroprotection due to their ability to modulate oxidative stress, neuroinflammation, and mitochondrial function. This narrative review aimed to evaluate the neuroprotective potential of nutraceuticals and their interactions with the microbiota-gut-brain axis in preventing age-related cognitive decline. A comprehensive search of the scientific literature using the PubMed, Scopus, and Web of Science databases was undertaken, focusing on publications during the period 2010-2025. Nutraceuticals, including vitamins, omega-3 fatty acids, coenzyme Q10, polyphenols, and isothiocyanates, exhibit neuroprotective properties through antioxidant, anti-inflammatory, and mitochondrial-support mechanisms. The gut microbiota plays a crucial role in regulating the bioavailability and efficacy of these compounds. Microbiome-based interventions, such as prebiotics, probiotics, and fecal microbiota transplantation demonstrate potential in modulating neuroinflammatory responses and supporting cognitive function. Nutraceutical and microbiome-targeted interventions represent promising, low-risk strategies for preventing cognitive decline. Their ability to modulate neuroinflammation and oxidative stress underscores their potential for future clinical applications. Further large-scale studies are needed to validate their efficacy and explore personalized approaches adapted to individual microbiome profiles.},
}

@article {pmid41875611,
year = {2026},
author = {Yang, Z and Zhang, F and Yang, S and Anayyat, U and Mo, Y and Ying, Y and Wang, X},
title = {Orally deliverable Perilla frutescens-derived nanovesicles as natural bioactive nanocarriers for colon-targeted colitis therapy via microenvironment reprogramming.},
journal = {Biomaterials advances},
volume = {184},
number = {},
pages = {214832},
doi = {10.1016/j.bioadv.2026.214832},
pmid = {41875611},
issn = {2772-9508},
abstract = {Effective oral therapy for inflammatory bowel disease (IBD) requires overcoming gastrointestinal barriers to modulate the dysregulated mucosal niche. Here, we present edible nanovesicles derived from Perilla frutescens (PLENs) as an intrinsically stable, bioactive nanotherapeutic. Multi-omics profiling defined a robust lipid-bilayer architecture encapsulating a synergistic cargo of proteins, miRNAs, and antioxidant metabolites. This structural integrity enabled PLENs to survive gastrointestinal transit and exhibit preferential fluorescence localization with prolonged retention in the inflamed colonic region, as indicated by in vivo imaging. Upon localization, PLENs executed a "dual-hit" therapeutic strategy: they reprogrammed the immune microenvironment, accompanied by reduced activation of the TLR4/MyD88-NF-κB axis and a phenotypic shift from pro-inflammatory M1 to reparative M2 macrophages. Concurrently, PLENs fundamentally restructured the gut ecosystem, accompanied by enrichment of taxa linked to saccharolytic fermentation and recovery of cecal short-chain fatty acids. Notably, fecal microbiota transplantation (FMT) further supported that this microbial remodeling contributed to the protective phenotype, highlighting the microbiome as an important component of efficacy.},
}

@article {pmid41875758,
year = {2026},
author = {Cui, H and Liu, Q and Leung, PSC and Chow, MW and Liu, SJ and Liu, B},
title = {Gut microbiota in pathogenesis and therapeutic potentials in rheumatoid arthritis.},
journal = {Current opinion in immunology},
volume = {100},
number = {},
pages = {102760},
doi = {10.1016/j.coi.2026.102760},
pmid = {41875758},
issn = {1879-0372},
abstract = {This review comprehensively explores the emerging roles of gut microbiota in the pathogenesis and therapeutic implications of rheumatoid arthritis (RA). Clinically, RA is a challenging autoimmune disease due to unclear pathology and limitations of conventional therapies. Recent studies highlight that gut dysbiosis - characterized by reduced microbial diversity, enrichment of proinflammatory taxa, and depletion of anti-inflammatory species - is an important contributor to RA. Mechanistically, gut microbiota dysregulation drives RA through molecular mimicry, metabolite-mediated inflammation, and immune cell migration. Therapeutic strategies targeting the gut-joint axis, including probiotics, high-fiber diets, Mediterranean dietary patterns, and fecal microbiota transplantation (FMT), demonstrate promise in restoring microbial homeostasis, enhancing intestinal barrier integrity, and suppressing proinflammatory cytokines. While preclinical and clinical studies underscore the potential of microbiota-based interventions, challenges such as standardization of FMT protocols and long-term safety require further investigation.},
}

@article {pmid41778924,
year = {2026},
author = {Lawenius, L and Hägg, D and Horkeby, K and Nilsson, KH and Wu, J and Grahnemo, L and Ohlsson, C and Sjögren, K},
title = {Gut microbiota transplantation from young adult mice fails to restore low bone and muscle mass in old mice.},
journal = {American journal of physiology. Endocrinology and metabolism},
volume = {330},
number = {4},
pages = {E461-E470},
doi = {10.1152/ajpendo.00522.2025},
pmid = {41778924},
issn = {1522-1555},
support = {2021 - 01739//Swedish Research Council/ ; 2020 - 01392//Swedish Research Council/ ; 2024 - 02412//Swedish Research Council/ ; ALFGBG-720331//ALF-agreement/ ; LFGBG-965235//ALF-agreement/ ; LU2021-0096//IngaBritt och Arne Lundbergs Forskningsstiftelse (Ingabritt and Arne Lundberg Research Foundation)/ ; LU2024-0110//IngaBritt och Arne Lundbergs Forskningsstiftelse (Ingabritt and Arne Lundberg Research Foundation)/ ; NNF 190C0055250//Novo Nordisk Foundation Center for Basic Metabolic Research (NovoNordisk Foundation Center for Basic Metabolic Research)/ ; NNF 22OC0078421//Novo Nordisk Foundation Center for Basic Metabolic Research (NovoNordisk Foundation Center for Basic Metabolic Research)/ ; KAW 2015.0317//Knut och Alice Wallenbergs Stiftelse (kawforskning)/ ; KAW 2020.0230//Knut och Alice Wallenbergs Stiftelse (kawforskning)/ ; ERC//European Union/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Aging/physiology ; *Fecal Microbiota Transplantation ; Male ; *Muscle, Skeletal ; Mice, Inbred C57BL ; *Bone Density/physiology ; Germ-Free Life ; *Bone and Bones ; Female ; Body Composition ; },
abstract = {Aging is associated with reduced lean and bone mass, as well as alterations in gut microbiota composition. We previously demonstrated that gut microbiota composition differs between young adult and old mice, and that transplanting gut microbiota from old donors into young germ-free mice reduces lean mass, but not bone mass, compared with transplantation from young adult donors. In this study, we investigated whether the reduced lean and bone mass observed in old mice could be restored through gut microbiota transplantation from young adult donors. Old mice (18-mo old) were treated with antibiotics to deplete their gut microbiota and subsequently transplanted with gut microbiota from either young adult (5-mo old) or old (21-mo old) donors. Recipient mice colonized with gut microbiota from young adult donors showed distinct beta and alpha diversity compared with those colonized with gut microbiota from old donors, demonstrating successful transplantation. However, no differences in lean or bone mass were observed between old mice transplanted with gut microbiota from young adult donors and those receiving gut microbiota from old donors. In conclusion, our findings demonstrate that gut microbiota composition differs in mice transplanted with young adult compared with old gut microbiota but neither reduced lean mass nor reduced bone mass in old mice can be restored through gut microbiota transplantation from young adult donors.NEW & NOTEWORTHY Aging is associated with reduced lean and bone mass and changes in gut microbiota (GM). We tested whether transplanting young adult GM could reverse these age-related conditions in old mice. GM transplantation resulted in distinct GM compositions between mice receiving young adult versus old donor GM, but neither lean nor bone mass was restored in old mice. These findings suggest that GM from young adult mice cannot restore musculoskeletal deficits in aging.},
}

Animals
*Gastrointestinal Microbiome/physiology
Mice
*Aging/physiology
*Fecal Microbiota Transplantation
Male
*Muscle, Skeletal
Mice, Inbred C57BL
*Bone Density/physiology
Germ-Free Life
*Bone and Bones
Female
Body Composition

@article {pmid41864269,
year = {2026},
author = {Melchiorri, S and Besutti, VM and Castagliuolo, I},
title = {Blastocystis spp. in Fecal Microbiota Transplantation: Evidence, Policy, and the Screening Paradox.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108548},
doi = {10.1016/j.ijid.2026.108548},
pmid = {41864269},
issn = {1878-3511},
abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection (rCDI). However, the detection of Blastocystis spp. in potential donors remains controversial and often leads to donor exclusion, despite uncertain pathogenicity. This review aims to critically evaluate the available evidence on Blastocystis spp. transmission through FMT, its clinical impact, and the implications of current donor screening strategies.

METHODS: A narrative review of the literature was performed using PubMed, Embase, and Web of Science. Studies reporting Blastocystis spp. detection in FMT donors or recipients, transmission events, clinical outcomes, diagnostic methods, and microbiome associations were included and analyzed.

RESULTS: Across published reports, 34 FMT recipients were exposed to Blastocystis spp.-positive donor material. Transmission was limited to common subtypes (ST1-ST3), was transient, and was not associated with adverse clinical outcomes or reduced efficacy of FMT for rCDI. No cases of symptomatic infection were reported. Frozen stool preparations appeared to abolish parasite viability. Molecular screening methods markedly increased detection rates compared with microscopy, frequently identifying low-burden colonization of uncertain clinical relevance. Available data suggest that Blastocystis spp. carriage may coexist with a healthy microbiome and does not negatively impact FMT outcomes.

CONCLUSIONS: Current evidence indicates that Blastocystis spp. transmission through FMT in immunocompetent adults is clinically benign. Routine donor exclusion based solely on Blastocystis spp. detection may therefore be overly restrictive. A risk-based approach incorporating parasite burden, subtype, host factors, and processing methods may better balance patient safety with donor availability, supporting more sustainable FMT programs.},
}

@article {pmid41867794,
year = {2026},
author = {Alviter-Plata, A and Ahmari, N and Gadient, J and Brammer-Robbins, E and Martyniuk, CJ and Zubcevic, J},
title = {Loss of Bone Marrow β1/β2-Adrenergic Receptors Reprograms Host-Microbiota Interactions and Protects Against Diet-Induced Obesity.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.05.707516},
pmid = {41867794},
issn = {2692-8205},
abstract = {The gut ecosystem is shaped by multiple factors with the immune system being one of the major determinants in shaping its composition in health and disease. On the other hand, the immune system regulates its responses through the action of the sympathetic nervous system (SNS) in part through beta-adrenergic receptors 1/2 (ADRB1/2). In the past years, a clear link has been established between the immune system, SNS, and the modification of nutrient absorption by the gut microbiota in the development of diet-induced obesity. We have previously shown in male mice transplanted with bone marrow cells ADRB1/2 knock-out mice (KD) showed mild immunosuppression and microbiota changes. Post-recovery, mice were challenged with high-fat diet (HFD) for two weeks ad libitum . Our findings show that KD mice are protected against diet-induced adiposity and weight gain. Additionally, these mice showed an increase in residual calorific values and a decreased expression of the fatty acid transporter FAT/CD36. Suggesting a decreased absorption of lipids in the KD mice. Gut microbiota analysis showed that KD microbiota composition on a HFD remained stable with a significant enrichment in the Bacteroidetes phylum , which is depleted in obesity. This was associated with a switch from triglycerides to diglyceride fecal profile. Moreover, microbiome culture showed a decrease in triglycerides after an incubation with 0.1% of HFD lipid extract. Suggesting a potential role of the Bacteroidetes phylum in the metabolism of these lipids. Our findings demonstrate not only that the gut microbiota can modify nutrient absorption and susceptibility to diet-induced obesity but also that the immune system contributes to selective depletion of microbial members that would otherwise thrive on dietary lipids. Revealing a novel mechanism by which host immunity sculpts the gut ecosystem in ways that influence metabolic outcomes.},
}

@article {pmid41868372,
year = {2026},
author = {Wang, Y and Zhang, Y and Cui, Y and Zhu, J and Wang, C and Wang, S and Xiao, X and Yang, L},
title = {Gut microbiota-derived EPA alleviates neuroinflammation associated with white matter injury by influencing H3K9ac/BDNF/TrkB pathway.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1711114},
pmid = {41868372},
issn = {1664-302X},
abstract = {BACKGROUND: The objective of our investigation was to explore the features of gut microbiota dysbiosis and the concentrations of gut metabolites in relation to white matter injury (WMI). Furthermore, we sought to evaluate the influence of gut dysbiosis on neuroinflammation in WMI via intestinal metabolites, and its contribution to pathogenesis.

METHODS: A cerebral hypoxia-ischemia-induced WMI model was established in 3-day-old Sprague-Dawley rats. Liquid chromatography-mass spectrometry/gas chromatography-mass spectrometry analyses and 16S rRNA gene sequencing were undertaken to ascertain WMI biomarkers. Mechanistic experiments were used to analyse activation of the H3K9ac/BDNF/TrkB pathway and neuroinflammation.

RESULTS: The analysis of 16S rRNA sequencing disclosed gut microbiota dysbiosis in WMI rats, quantified using linear discriminant analysis effect size. Overall, 341 differentially expressed metabolic markers between the WMI and Sham groups were discovered. The Kyoto Encyclopedia of Genes and Genomes network enhancement evaluation revealed significant downregulation of 20 metabolic processes in the WMI group, which is strongly related to changes in fecal microbial metabolites, and the synthesis process of unsaturated fatty acids was the most significant. Gut microbiota dysbiosis may influence WMI by downregulating metabolites such as eicosapentaenoic acid (EPA). Fecal microbiota transplantation increased EPA concentration in the brain tissue of WMI rats. Gut microbiota-derived EPA promoted H3K9ac and BDNF/TrkB expression and inhibited the transcription of pro-inflammatory TNF-α and IL-1β molecules. These EPA-mediated effects were reversed by TrkB inhibition.

CONCLUSION: WMI induces gut dysbiosis involving down-regulation of unsaturated fatty acid synthesis. Fecal microbiota transplantation leads to increased levels of EPA. Gut microbiota-derived EPA increases levels of acetylated histone H3K9ac, causes activation of the BDNF/TrkB pathway, reduces neuroinflammation, and improves WMI-associated myelination disorders. It provides a basis for targeted treatment of white matter injury in the future.},
}

@article {pmid41869071,
year = {2026},
author = {Schotz, KM and Alizadeh, M and Rapoport, AP and Ravel, J and Von Rosenvinge, EC},
title = {Faecal microbiota transplant for chronic norovirus infection: a case report of donor microbiota engraftment without clinical success.},
journal = {Gastroenterology report},
volume = {14},
number = {},
pages = {goag015},
pmid = {41869071},
issn = {2052-0034},
}

@article {pmid41870087,
year = {2026},
author = {Wang, X and Wu, W and Yang, B and Liu, Y and Xu, Y and Wang, L and Lv, X and Gao, J and Lu, M and Yu, A and Li, N and Chen, Q and Lu, L and Zhao, D},
title = {Additive effects of fecal microbiota transplantation and infliximab on gut microbiome and metabolome in refractory inflammatory bowel disease patients.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0077425},
doi = {10.1128/msystems.00774-25},
pmid = {41870087},
issn = {2379-5077},
abstract = {UNLABELLED: Fecal microbiota transplantation (FMT) is an emerging therapy for inflammatory bowel disease (IBD), yet its efficacy in patients refractory to conventional treatments and its underlying mechanisms require further elucidation. We studied 37 IBD patients (15 ulcerative colitis [UC], 22 Crohn's disease [CD]) refractory to conventional therapies and 16 healthy donors. FMT monotherapy from a single donor induced week-4 clinical response in 12 UC and 9 biologic-naïve CD patients, with all responders sustaining remission and most achieving endoscopic remission by week 14. Integrated multi-omics revealed FMT restored microbial diversity and profoundly reorganized host-microbiota-metabolite networks. In nine refractory CD patients (7 infliximab [IFX] non-responders, 2 FMT non-responders), IFX-FMT combination led to week-4 response in 6 patients, all of whom attained clinical and endoscopic remission by week 14, with more complete microbial-metabolic restoration than monotherapy. Our findings establish that FMT induces remission in refractory IBD via ecosystem network rewiring, and that IFX-FMT exhibits additive effects, supporting further trials of microbiome-directed adjunctive strategies.

IMPORTANCE: This study provides mechanistic and clinical insights into the therapeutic effects of fecal microbiota transplantation (FMT) in inflammatory bowel disease (IBD), particularly when combined with the anti-tumor necrosis factor (anti-TNF) biologic infliximab (IFX). While both FMT and IFX achieve response in approximately 60% of IBD patients, their combined influence on the gut microbial and metabolic landscape in refractory disease has been poorly understood. Here, we demonstrate that FMT monotherapy restores gut microbial diversity and reconfigures host-microbiota-metabolite networks, correlating with clinical and endoscopic remission in patients refractory to conventional treatments. Furthermore, in Crohn's disease patients unresponsive to either therapy alone, combined IFX-FMT induced more complete microbial and metabolic normalization and achieved remission where monotherapy had failed. These findings reveal ecosystem-level network rewiring as a central mechanism of FMT efficacy and establish the additive potential of combining microbiome-targeted and immunomodulatory therapies. This work supports the development of microbiome-informed adjunctive strategies for severe or refractory IBD, highlighting an actionable path toward personalized, mechanism-based treatment regimens.

CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT07149441.},
}

@article {pmid41870947,
year = {2026},
author = {Zhang, L and Zeng, X and Ma, C and Wei, Y and Wang, W and Liu, T and Li, W},
title = {Acupoint catgut embedding ameliorates laparotomy-induced cognitive decline in aged mice by restoring gut microbiota.},
journal = {Neuroreport},
volume = {},
number = {},
pages = {},
doi = {10.1097/WNR.0000000000002255},
pmid = {41870947},
issn = {1473-558X},
support = {YQJH2023028//Program for Young Talents of Basic Research in Universities of Heilongjiang Province (YQJH2023028)/ ; },
abstract = {BACKGROUND: Postoperative cognitive dysfunction (POCD), a common neurological complication in elderly patients, significantly impairs recovery. Emerging evidence suggests the gut microbiota is involved in its pathogenesis. This study aimed to determine whether acupoint catgut embedding (ACE) could alleviate POCD by modulating the gut microbiota in aged mice after laparotomy.

METHODS: Eighteen-month-old male C57BL/6J mice underwent laparotomy on day 8 (excluding the Sham group). The ACE group received ACE treatment, while the anesthesia and surgery group served as surgical controls. The fecal microbiota transplantation (FMT)-ACE and FMT-AS groups received FMT from corresponding donors. Additional groups received oral indole-3-propionic acid (IPA) or vehicle-treated surgery. Hippocampal inflammation and blood-brain barrier proteins were assessed on day 9; cognitive function and intestinal markers on day 15.

RESULTS: Cognitive function was significantly improved in the ACE, FMT-ACE, and IPA groups. ACE and FMT-ACE treatments specifically elevated fecal g-Clostridia_UCG-014 abundance and serum IPA levels. These changes were accompanied by suppressed hippocampal toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling and proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β], together with elevated tight junction proteins (occludin, claudin-5). Furthermore, colonic aryl hydrocarbon receptor (AhR) and IL-22 were upregulated, while serum lipopolysaccharide and diamine oxidase were reduced. Accordingly, IPA treatment mirrored the key anti-inflammatory and barrier-protective effects.

CONCLUSION: ACE alleviates POCD probably by modulating gut microbiota, specifically increasing g-Clostridia_UCG-014 abundance and metabolite IPA. These effects are potentially mediated by dual pathways: (a) suppression of neuroinflammation via TLR4/NF-κB signaling, and (b) enhancement of gut barrier integrity via AhR/IL-22 axis. Our findings highlight the therapeutic potential of ACE in targeting the gut-brain axis for POCD management.},
}

@article {pmid41871875,
year = {2026},
author = {Zhang, Y and Xu, X and Wang, S and Yin, X and Zhang, B and Zhu, Z and Ji, R and Zhu, J and He, H and Cheng, S and Han, Z and Xie, T and Zhang, X and Wang, Y and Shen, S and Kou, Y and Bao, S and Liu, Y and Cao, B and Bonny, C and Guo, X and Segal, E and Tan, Y and Shen, L and Peng, Z},
title = {Fecal microbiota transplantation combined with anti-PD-1 therapy in refractory microsatellite-stable gastric cancer: a phase I feasibility and safety study.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {3},
pages = {},
doi = {10.1136/jitc-2025-013823},
pmid = {41871875},
issn = {2051-1426},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; *Stomach Neoplasms/therapy/drug therapy ; Middle Aged ; Aged ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Feasibility Studies ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Adult ; },
abstract = {BACKGROUND: The discovery and therapeutic application of immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes in cancer treatment. However, the response rate is still low in gastrointestinal (GI) cancers. The gut microbiome's impact on immune modulation is a promising area for overcoming resistance to immunotherapy.

METHODS: This study (NCT04130763) is an open-label, single-arm, single-center, phase I study assessing the safety and efficacy of fecal microbiota transplantation (FMT) from healthy donors in 10 patients with advanced GI cancer resistant to anti-programmed death-ligand 1 (PD-(L)1) treatment. 10 patients with histologically confirmed, unresectable, or metastatic GI cancers (8 gastric, 2 colorectal) who were refractory to anti-PD-(L)1 treatment were enrolled. Patients received initial FMT treatment via oral capsules (60 capsules), followed by a combination therapy phase, where maintenance FMT (10 capsules per treatment) was paired with nivolumab at 3 mg/kg every 2 weeks for six cycles. Serial biomarker assessments were conducted through both fecal and blood sampling.

RESULTS: The combination of FMT and anti-PD-1 treatment was well tolerated with no serious adverse events. The objective response rate was 20% and the disease control rate was 40%. Clinical benefits were associated with colonization of donor-derived immunogenic microbes, and an activated immune status reflected by peripheral immune cell populations. Moreover, microbial signatures were identified for anti-programmed cell death protein-1 (PD-1) responsiveness and validated in an independent cohort.

CONCLUSIONS: This phase I study demonstrates the feasibility and safety of combining FMT with anti-PD-1 therapy in patients with ICI-refractory gastric cancer. The observed preliminary efficacy signals and identified microbial signatures generate hypotheses for future trials to investigate microbiome-based approaches to enhance immunotherapy efficacy.

TRIAL REGISTRATION NUMBER: NCT04130763.},
}

Humans
*Fecal Microbiota Transplantation/methods
Male
Female
*Stomach Neoplasms/therapy/drug therapy
Middle Aged
Aged
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
Feasibility Studies
*Programmed Cell Death 1 Receptor/antagonists & inhibitors
Adult

@article {pmid41862794,
year = {2026},
author = {Tian, M and Zeng, X and Zhong, Y and Ma, B and Feng, Y and Wu, X and Liao, Y and Xu, Y and Chen, T and Tan, B},
title = {Combination of Tripterygium glycosides and Lactobacillus paracasei sensitises epithelial ovarian cancer to cisplatin via downregulating Keap1-Nrf2-GPX4 signalling pathway.},
journal = {Cellular & molecular biology letters},
volume = {},
number = {},
pages = {},
doi = {10.1186/s11658-025-00850-3},
pmid = {41862794},
issn = {1689-1392},
support = {82160766//National Natural Science Foundation of China/ ; 2024SSY07061//Jiangxi Province Key Laboratory of bioengineering drugs/ ; 20242BAB20417//Youth Fund Project of Jiangxi Provincial Natural Science Foundation/ ; },
abstract = {BACKGROUND: Epithelial ovarian cancer (EOC) is a highly heterogeneous malignancy with significant morbidity and mortality, and cisplatin (DDP) resistance remains a major obstacle in its treatment. Previous studies suggest that Tripterygium glycosides (TG), derived from Tripterygium wilfordii, may enhance EOC chemo-sensitivity to DDP, potentially involving gut microbiota, though the underlying mechanisms remain to be fully elucidated.

PURPOSE: This study sought to determine how TG enhanced chemotherapy sensitivity in EOC and to examine the involvement of gut microbiota in this process.

STUDY DESIGN: Experimental research in vivo models was conducted, including fecal microbiota transplantation (FMT) from healthy controls and validation assays with Lactobacillus paracasei.

METHODS: TG were administered alone or combined with FMT to evaluate their impact on DDP sensitivity in EOC. Mechanistic studies focused on the Keap1-Nrf2-GPX4 signalling pathway and ferroptosis induction. L. paracasei was co-administered with TG to assess synergistic effects, while Nrf2 pathway activation was tested to confirm its regulatory role.

RESULTS: TG significantly enhanced DDP sensitivity in EOC, either alone or synergistically with FMT. Mechanistically, TG inhibited the Keap1-Nrf2-GPX4 axis, inducing tumor ferroptosis. Gut microbiota, particularly the probiotic Lactobacillus, contributed to this effect: L. paracasei combined with TG amplified DDP cytotoxicity in EOC cells. Conversely, Nrf2 pathway activation attenuated the synergistic effect.

CONCLUSION: TG sensitises EOC to DDP by suppressing the Keap1-Nrf2-GPX4 pathway to trigger ferroptosis, with gut microbiota (e.g., L. paracasei) playing a synergistic role. Combining TG and probiotics may offer a promising and innovative method to improve chemotherapy efficacy in EOC, offering a foundation for future therapeutic development.},
}

@article {pmid41863247,
year = {2026},
author = {Feng, S and Huang, Q},
title = {Microbiota-driven Immunopathogenesis in Systemic Lupus Erythematosus: Cross-site Mechanisms and Intervention Strategies.},
journal = {Current molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115665240433654260209063544},
pmid = {41863247},
issn = {1875-5666},
abstract = {Systemic lupus erythematosus (SLE) is a complex autoimmune disease whose pathogenesis involves intricate interactions with the human microbiota. Accumulating evidence reveals significant compositional and functional dysbiosis in the gut, oral, skin, and vaginal microbiota of SLE patients compared to healthy individuals. These dysbioses actively contribute to disease development and progression through a multitude of mechanisms. These include impaired epithelial barrier integrity, exemplified by the "leaky gut" phenomenon, which facilitates the translocation of microbial antigens. Molecular mimicry, where microbial antigens share structural similarities with host self-antigens, triggers the production of cross-reactive autoantibodies. Furthermore, dysregulated production of microbial metabolites, such as short-chain fatty acids, tryptophan derivatives like tryptamine, and histamine, directly modulates host immune cell function, promotes inflammatory responses, and influences epigenetic regulation. The causal role of specific microbiota in SLE is substantiated by experimental models, including fecal microbiota transplantation studies where transfer of SLE-associated microbiota can recapitulate autoimmune features in recipient germ-free mice, and mono-colonization with pathobionts like Ruminococcus gnavus or Staphylococcus aureus can drive specific aspects of the disease. This growing understanding has paved the way for novel microbiota-targeting interventions. Strategies such as dietary modifications, probiotic and prebiotic supplementation, and fecal microbiota transplantation show considerable promise in preclinical and early clinical studies for restoring microbial homeostasis, rebalancing dysregulated immune responses, and alleviating disease activity. However, challenges in patient-specific variability, understanding precise mechanisms, and ensuring longterm safety remain. Future research must focus on delineating detailed causal pathways, validating efficacy in large-scale trials, and ultimately developing personalized microbiota-targeting interventions to improve SLE management and patient outcomes.},
}

@article {pmid41863409,
year = {2026},
author = {Kaur, S and Bhandari, N and Mahajan, S and Mehta, D and Chauhan, S and Kumar, V and Rohilla, M and Mehta, S and Dhankhar, S},
title = {Molecular Pathways of Microbiota-derived Neuromodulation: An Integrative View.},
journal = {Current neurovascular research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672026427392260131184931},
pmid = {41863409},
issn = {1875-5739},
abstract = {INTRODUCTION: The gut microbiota, also called "the forgotten organ", is a complex and dynamic ecosystem of microorganisms that is fundamental to human physiology, neurobiology, and disease. This review examines the intricate relationships between the gut microbiota and the nervous system via the microbiota-gut-brain (MGB) axis. It discusses their endocrine, immunological, and neural pathways.

METHODS: A thorough literature search was performed across databases including PubMed, Scopus, Web of Science, and Google Scholar, using keywords such as "gut microbiota," "microbiota- gut-brain axis," "neuromodulation," "serotonin," "dopamine," "GABA," "norepinephrine," "prebiotics," "probiotics," and "faecal microbiota transplantation"..

RESULTS: This article explains how the gut microbiota impacts significant body's chemical messengers such as serotonin, dopamine, GABA, and norepinephrine. These are essential for brain functioning. All of these diseases have evidence linking inflammation of the gut and the brain. Furthermore, gut dysbiosis has been responsible for some of the most serious disorders of mankind through pandemics and plagues.

DISCUSSION: Moreover, prebiotics, probiotics, faecal microbiota transplantation (FMT), synbiotics, diet, and bioactive substances such as curcumin and flavonoids are new treatment approaches. These strategies help bring back a normal balance of gut microbes for mental and neurological health. Even though preclinical studies have shown promise, bringing it to humans is not simple. Issues like the strain, the individual, and sustained use make it a substantial challenge.

CONCLUSION: Future directions of work should combine and focus human-based research efforts with precise and personalized microbiome modulation, allowing us to leverage the gut-brain axis therapeutically.},
}

@article {pmid41863784,
year = {2026},
author = {Giannakogeorgou, A and van den Ende, T and Verhaar, BJH and de Clercq, N and van Laarhoven, HWM and Nieuwdorp, M},
title = {Targeting the gut microbiota as treatment for obesity and cancer cachexia.},
journal = {Expert opinion on emerging drugs},
volume = {},
number = {},
pages = {},
doi = {10.1080/14728214.2026.2650180},
pmid = {41863784},
issn = {1744-7623},
abstract = {INTRODUCTION: Obesity and cancer cachexia represent two seemingly contrasting yet interrelated ends of the metabolic disorder spectrum, both characterized by disrupted energy homeostasis, inflammation and neuroendocrine dysfunction, and associated with increased morbidity and mortality. Existing treatments often fail to address the complex underlying pathophysiological mechanisms. Emerging research highlights the role of the gut microbiome in the pathophysiology of both conditions and how it can serve as a novel therapeutic target.

AREAS COVERED: This review explores shared and distinct pathways linking obesity and cancer cachexia. Key systems discussed include the gut-brain axis as well as skeletal muscle and adipose tissue metabolism. We discuss how the gut microbiota influences these processes through (diet-derived) gut microbial metabolites that affect specific signaling pathways. The review evaluates the efficacy and limitations of current anti-obesity and cachexia therapies and summarizes clinical and preclinical interventions targeting the gut microbiome, including pre-, pro-, postbiotics and fecal microbiota transplantation.

EXPERT OPINION: The gut microbiota holds potential as a therapeutic target in metabolic diseases, offering opportunities for precision medicine based on microbial and metabolic profiles. While early microbiota-based therapies show promise, further investigation into mechanistic pathways and novel engineered microbiota is essential to develop effective treatments for obesity and cachexia.},
}

@article {pmid41864031,
year = {2026},
author = {Zhai, Z and Yang, Y and Xu, Y and Fu, Q and Chen, S and Wu, Z},
title = {Polydisperse polystyrene microplastics exacerbate colitis through gut microbiota-butyrate-PPARγ axis disruption in mice.},
journal = {Journal of hazardous materials},
volume = {507},
number = {},
pages = {141722},
doi = {10.1016/j.jhazmat.2026.141722},
pmid = {41864031},
issn = {1873-3336},
abstract = {The escalating global prevalence of inflammatory bowel disease (IBD) parallels widespread dietary exposure to microplastics (MPs), yet causal mechanisms linking polydisperse MPs to colitis remain elusive. Here, we show that polydisperse polystyrene microspheres (PS-MS) exacerbate dextran sulfate sodium (DSS)-induced colitis in mice by disrupting a microbiota-butyrate-PPARγ signaling axis. Mechanistically, PS-MS treatment alone does not directly induce colon inflammation in healthy mice; however, it suppresses intestinal Muc2 protein expression and impairs the mucus barrier by reducing the abundance of Lachnospiraceae_NK4A136_group and butyrate levels, thereby inhibiting PPARγ signaling and aggravating colitis. An antibiotic cocktail (ABX)-mediated microbiota ablation abolishes PS-MS-induced colitis aggravation, whereas fecal microbiota transplantation (FMT) from PS-MS-exposed donors transmits susceptibility to antibiotic-treated mice, confirming microbiota-dependent pathogenesis. Exogenous sodium butyrate supplementation restores mucosal homeostasis via PPARγ activation, as evidenced by the abolition of protection following administration of the PPARγ antagonist GW9662, and by the comparable efficacy of the PPARγ agonist 5-ASA. Our findings establish the microbiota-butyrate-PPARγ axis as a critical target for counteracting the adverse effects of environmental MPs and propose butyrate-boosting therapies as a translatable strategy against IBD.},
}

@article {pmid41864264,
year = {2026},
author = {Merrick, B and Mullish, BH and Goldenberg, SD and Khanna, S and Ahuja, V and Hvas, CL and Makharia, GK and Williams, HRT},
title = {A global evaluation of the use of faecal microbiota transplant (FMT).},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108574},
doi = {10.1016/j.ijid.2026.108574},
pmid = {41864264},
issn = {1878-3511},
abstract = {BACKGROUND: Faecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridioides difficile infection (CDI); its use is increasingly being investigated for other indications. Although regional surveys and national registries have provided insight into local practices, a comprehensive global overview of FMT access, implementation and governance is lacking.

METHODS: A survey regarding key aspects related to FMT use was disseminated electronically to members of the World Gastroenterology Organisation, European FMT Network, and International Society of Infectious Diseases. Responses were analysed both descriptively and using appropriate statistical methods.

FINDINGS: 80 responses were obtained from 55 countries. FMT was available in significantly more Tier 1/2, than Tier 3/4, nations (24/28 vs 8/27; p<0.001). In countries lacking access to FMT reasons included: lack of expertise/infrastructure; financial constraints; regulatory uncertainty; and perceived lack of clinical need. Most countries using FMT employed both upper and lower gastrointestinal administration routes; 18/32 (56%) used capsulised FMT. Almost all countries with access to FMT used it to treat CDI, albeit with different thresholds for the number of CDI episodes prior to use. There were many non-CDI indications for FMT in current use. Payment for stool donation was reported by 10 countries.

INTERPRETATION: This is the first global overview of FMT availability and governance, highlighting substantial international inequities and considerable heterogeneity in regulation, clinical use, donor screening, and cost. Standardisation of practice and targeted support for lower income countries is needed to ensure equitable access and to promote safe, high-quality delivery as FMT and microbiome-based therapeutics continue to evolve.},
}

@article {pmid41861987,
year = {2026},
author = {Ramirez-Amoros, C and Amesty, V and Martínez, L and Martínez Urrutia, MJ and Vilanova-Sánchez, A},
title = {Post-Pubertal Outcomes in Patients with Cloacal Malformations: Colorectal, Urological, and Gynaecological Function with Patient-Reported Sexual Outcomes.},
journal = {Journal of pediatric surgery},
volume = {},
number = {},
pages = {163087},
doi = {10.1016/j.jpedsurg.2026.163087},
pmid = {41861987},
issn = {1531-5037},
abstract = {INTRODUCTION: Long-term functional outcomes in patients with cloacal malformations remain poorly described. This study reports long-term outcomes from a tertiary referral center.

METHODS: Retrospective review of female patients with cloacal malformations treated between 1980 and 2010. Colorectal, urological, and gynaecological outcomes were obtained from medical records. Sexual function was assessed using a validated female sexual health questionnaire and compared with 15 healthy controls.

RESULTS: Eleven women were included, with a mean age at follow-up of 24.77 ± 7.41 years. Associated anomalies were present in 73% of patients, including spinal anomalies in 27%. All patients underwent neonatal stoma creation and closure, the latter at a median age of 2.55 (1.61-3.72) years. Faecal continence was achieved in 73% of patients at a mean age of 10.4 ± 3.1 years; one patient required laxatives and five required enemas. All patients achieved urinary dryness. A Mitrofanoff procedure was required in 36%, and one patient underwent bladder augmentation. End-stage renal disease developed in 36%, with three patients undergoing renal transplantation and one awaiting transplant. Three patients (27%) required vaginoplasty, and four (36%) later underwent external genitoplasty. Müllerian anomalies were present in 73%, and 91% menstruated. Sexual function assessment demonstrated increased fear of sexual activity, avoidance due to perineal appearance, reduced excitation, and greater difficulty with vaginal penetration compared with controls.

CONCLUSION: Most patients in our institution with cloacal malformations achieve satisfactory faecal and urinary continence following reconstruction. Renal dysfunction and impaired sexual function remain relevant long-term issues, supporting the need for lifelong multidisciplinary follow-up.},
}

@article {pmid41782164,
year = {2026},
author = {Sørensen, KM and Jensen, CH and Möller, S and Qvist, N and Andersen, DC and Sørensen, JA},
title = {Repairing Peri-Anal Fistulas with regenerative cell therapeutics: study protocol for a double-blinded randomized controlled phase I-II trial from Denmark (REP-PAF).},
journal = {Trials},
volume = {27},
number = {1},
pages = {},
pmid = {41782164},
issn = {1745-6215},
support = {NNF21OC0071847//Novo Nordisk Fonden/ ; NNF19OC0055353//Novo Nordisk Fonden/ ; },
mesh = {Humans ; *Rectal Fistula/surgery/physiopathology/diagnosis ; Double-Blind Method ; Denmark ; *Adipose Tissue/cytology/transplantation ; Treatment Outcome ; Randomized Controlled Trials as Topic ; Clinical Trials, Phase II as Topic ; Quality of Life ; Time Factors ; Debridement/adverse effects ; Wound Healing ; *Stem Cell Transplantation/adverse effects/methods ; Transplantation, Autologous ; Female ; *Anal Canal/surgery/physiopathology/diagnostic imaging ; },
abstract = {BACKGROUND: Surgical treatment of high anal fistulas is challenging and associated with a relatively high rate of complications and failure. Stem cell therapy has shown promising results for fistulas associated with Crohn's disease but remains less studied in cryptoglandular fistulas. This clinical trial is being performed to evaluate the outcome of treating complex cryptoglandular perianal fistulas (PAFs) using minimal surgical debridement combined with either non-cultured (autologous) or cultured (allogeneic) adipose-derived regenerative cells (ADRCs). The primary outcome is the clinical healing rate after 12 months. Secondary outcomes include functional outcomes regarding quality of life and anal continence (measured by the 36-Item Short Form Health Survey [SF-36] and the Wexner Fecal Incontinence Score), risk factors for fistula recurrence, radiological healing assessed by magnetic resonance imaging, and comparison of autologous versus allogeneic ADRCs with respect to cell characterization, immune responses, and efficacy.

METHODS: This is a double-blinded, randomized interventional non-inferiority, phase I-II clinical trial using two approved investigational medicinal products. The study will be conducted at the surgical department, Odense University Hospital OUH, in Odense, Denmark. Inclusion criterion is an adult patient (≥ 18 years) with complex PAF (high transsphincteric or suprasphincteric), involving more than 30% of the anal sphincter. Key exclusion criteria are ongoing suppuration, simple anal fistula, ano- or rectovaginal fistula, inflammatory bowel disease, body mass index (BMI) of < 18.5 kg/m[2], known allergy to penicillin or streptomycin, pregnancy, and verified syphilis, human immunodeficiency virus (HIV), or hepatitis on screening test. The primary investigator (PI) is responsible for participants' recruitment. Eligible patients will undergo 1-day surgery, including debridement of the fistula tract and closure of the internal orifice, liposuction from the anterior abdominal wall, injection of 30-40 mL of autologous microfat around the fistula tract, and injection of 30 million stem cells (either autologous ADRCs or allogeneic ADRC001) according to randomization (1:1 allocation ratio). Patients who receive treatment will attend follow-up visits at 3, 6, and 12 months postoperatively. Serious adverse events will be reported including large abscess formation, wound dehiscence causing fecal incontinence, sepsis, major bleeding, and serious allergic reactions. The trial has been approved by the European Medicines Agency EMA and is monitored by the Good Clinical Practice (GCP) Unit at OUH. A total of 75 patients will be included. Recruitment began in October 2024, with a planned duration of 3 years.

DISCUSSION: The trial intervention is designed as a minimally invasive treatment with the potential to shorten and ease recovery, enable a quicker return to daily activities and work, and avoid sphincter damage, thereby preserving function. The trial is expected to provide evidence on whether allogeneic ADRCs combined with microfat are a viable alternative to autologous ADRCs with microfat for the treatment of PAF.

TRIAL REGISTRATION: Clinical Trials Information System (CTIS) EU CT 2022-502659-73-01. Registered on 18 November 2023.

CLINICALTRIALS: org NCT0 6303752. Registered on 25 February 2024.},
}

Humans
*Rectal Fistula/surgery/physiopathology/diagnosis
Double-Blind Method
Denmark
*Adipose Tissue/cytology/transplantation
Treatment Outcome
Randomized Controlled Trials as Topic
Clinical Trials, Phase II as Topic
Quality of Life
Time Factors
Debridement/adverse effects
Wound Healing
*Stem Cell Transplantation/adverse effects/methods
Transplantation, Autologous
Female
*Anal Canal/surgery/physiopathology/diagnostic imaging

@article {pmid41856839,
year = {2026},
author = {Suchodolski, JS and Toresson, L},
title = {Microbiome Modulation in Veterinary Medicine: From Diet to Fecal Microbiota Transplantation.},
journal = {The Veterinary clinics of North America. Small animal practice},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cvsm.2026.01.009},
pmid = {41856839},
issn = {1878-1306},
abstract = {The intestinal microbiome plays a crucial role in host health. As intestinal dysbiosis can have different underlying causes, multimodal therapeutic approaches are often necessary. Dietary modulation potentially combined with fibers should be the first-line approaches in all patients with acute or chronic enteropathy and help modulate the microbiome. A subset of animals with chronic intestinal disease have marked dysbiosis that results in abnormal microbial function and reflects underlying mucosal pathology, which often persists in chronic inflammatory enteropathy. Fecal microbiota transplantation can be a useful adjunct treatment of chronic disorders, but in patients with severe dysbiosis, repeated treatments are likely needed.},
}

@article {pmid41858792,
year = {2026},
author = {Raber, J and Sharpton, TJ},
title = {Diet, gut microbiome, and cognition in neurodegeneration: a review and methodological framework.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1771904},
pmid = {41858792},
issn = {1663-4365},
abstract = {The gut microbiome influences brain function through the gut-brain axis via synthesis of neurotransmitters, production of metabolites affecting epithelial barrier integrity and immune modulation and signaling through the vagus nerve. In humans, microbiome diversity reflects healthy aging and predicts survival, while dysbiosis is increasingly implicated in neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ALS. Fecal transplant studies in germ-free mice demonstrate that microbiome alterations are sufficient to induce cognitive and neuropathological phenotypes, supporting causality in preclinical models. Genetic risk factors and environmental exposures affect both neurodegeneration risk and microbiome composition. In this review, we synthesize evidence from human cohorts and preclinical models on the gut-brain axis in cognitive health and disease. We then present a methodological framework for diet-microbiome-cognition research, addressing causal inference through mediation analysis, supervised approaches for deriving diet scores, validation strategies, and individual heterogeneity. This framework can guide development of microbiome-targeted dietary interventions to improve cognitive outcomes.},
}

@article {pmid41859112,
year = {2026},
author = {Chen, H and Lou, G and Meng, F and Zhang, Y and Kuang, H and Yang, D},
title = {Critical role of reproductive tract microbiota and derived metabolites in inflammation, tumor immunity, and tumorigenesis of gynecological cancers: a narrative review.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1734792},
pmid = {41859112},
issn = {1664-3224},
mesh = {Humans ; Female ; *Genital Neoplasms, Female/metabolism/immunology/microbiology/therapy/etiology ; Animals ; *Microbiota/immunology ; *Carcinogenesis/immunology ; Inflammation/immunology/metabolism/microbiology ; *Gastrointestinal Microbiome/immunology ; *Genitalia, Female/microbiology/immunology ; },
abstract = {Gynecological malignancies, including ovarian, cervical, and endometrial cancers, present significant clinical challenges due to the epidemiological complexity and limitations in current therapeutic strategies. Emerging evidence highlights the critical role of the microbiome and its metabolites in modulating tumor initiation, progression, and treatment responses. This review explores the intricate mechanisms through which gut and reproductive tract microbiota influence gynecological cancers via immune regulation, metabolic reprogramming, and epigenetic modifications. Key microbial metabolites, such as short-chain fatty acids, bile acids, and estrogen-metabolizing intermediates, serve as molecular bridges in host-microbe communication, impacting chemotherapy resistance and immunotherapy efficacy. Furthermore, we discuss the translational potential of microbiome-targeted interventions, including probiotics, fecal microbiota transplantation, and precision microbial therapies, as innovative approaches for diagnosis, prognosis, and treatment. Understanding the microbiota-reproductive axis offers novel insights into overcoming therapeutic resistance and improving patient outcomes in gynecologic oncology.},
}

Humans
Female
*Genital Neoplasms, Female/metabolism/immunology/microbiology/therapy/etiology
Animals
*Microbiota/immunology
*Carcinogenesis/immunology
Inflammation/immunology/metabolism/microbiology
*Gastrointestinal Microbiome/immunology
*Genitalia, Female/microbiology/immunology

@article {pmid41859191,
year = {2026},
author = {Su, Y and Xia, Y},
title = {Gut microbiota dysbiosis and depression: Bidirectional interactions, mediating pathways, and microecological therapeutics.},
journal = {Current research in food science},
volume = {12},
number = {},
pages = {101372},
pmid = {41859191},
issn = {2665-9271},
abstract = {The microbiota-gut-brain axis (MGBA) is increasingly recognized as a key target for ameliorating major depressive disorder (MDD). This review systematically synthesizes evidence on the bidirectional relationship between gut microbiota dysbiosis and MDD, and delineates the core mechanisms-such as neuroinflammation, neurotransmitter metabolism, and hypothalamic-pituitary-adrenal (HPA) axis dysregulation-through which this axis influences depressive pathogenesis. Further, the intestinal microbiota characteristics related to MDD, the main regulatory pathways, and the potential efficacy of microbiome-targeted intervention measures-including psychobiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary strategies-were sorted out. In the clinical assessment and drug research of depression, the assessment tools are mainly divided into two categories: clinician-rated and self-reported. These two types are often used together to provide multi-dimensional evidence of therapeutic efficacy. Evidence suggests that stress-related intestinal permeability may initiate gut dysbiosis, which in turn can impair barrier function, promote neuroinflammation, disrupt neurotransmitter synthesis, and overactivate the HPA axis, potentially exacerbating depressive symptoms. Interventions targeting the gut microbiota may help reshape microbial communities, increase short-chain fatty acids (SCFAs) and 5-Hydroxytryptamine (5-HT), and dampen inflammatory and stress responses, thereby offering a promising, non-pharmacological avenue for alleviating MDD. This review not only offers a theoretical foundation for microbiota-based therapeutics in MDD but also highlights pathways toward developing safe, effective non-pharmacological strategies for depression management.},
}

@article {pmid41859453,
year = {2026},
author = {Cao, L and Zhu, W},
title = {Insights from the high-altitude animal gut adaptation model: mechanisms of obesity regulation via microbiota-derived metabolite homeostasis and the gut-X axis.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1795452},
pmid = {41859453},
issn = {1664-302X},
abstract = {The unique environmental conditions at high altitudes drive the gut microbiota of resident animals to develop distinct structural and functional traits, thereby offering an ideal natural model for investigating the synergistic adaptation of hosts and microorganisms to extreme environmental stressors. This review systematically expounds the mechanism of metabolic adaptation of gut microbiota to high-altitude through the phenotypic characteristics of "high productivity and low inflammation," and understands the mediating effect of short-chain fatty acids and secondary bile acids, which are derived metabolites of flora. SCFAs can enhance the intestinal barrier, regulate the function of immune cells, act on the gut-brain axis, and then affect the feeding behavior. SBAs, as signal molecules, regulate the lipid and energy metabolism of the host through the gut-liver axis. This division of labor and coordination, driven by different metabolites and achieved through specific gut-X axis pathways, constitutes a microecological regulatory network that enables the host to maintain metabolic homeostasis in high-altitude areas. Understanding this natural model can reveal the role of "flora metabolite organ axis" in maintaining health. It can also provide reference direction for obesity intervention caused by high-fat diet (HFD) and other factors, such as regulating the function of gut microbiota through strategies such as dietary regulation, probiotics and prebiotics supplementation, and fecal microbiota transplantation (FMT), and regulating the specific gut-X axis pathway, so as to restore metabolic balance.},
}

@article {pmid41860558,
year = {2026},
author = {Bloom, P and Khanna, S},
title = {Fecal microbiota transplantation in chronic liver disease: Current and future state of the art.},
journal = {Hepatology communications},
volume = {10},
number = {4},
pages = {},
doi = {10.1097/HC9.0000000000000927},
pmid = {41860558},
issn = {2471-254X},
mesh = {*Fecal Microbiota Transplantation/methods/trends/adverse effects ; Humans ; Gastrointestinal Microbiome ; *Liver Diseases/therapy ; Chronic Disease ; },
abstract = {Chronic liver diseases are associated with changes in gut microbiome composition and function. Early data suggest that fecal microbiota transplantation (FMT) may treat several chronic liver diseases, especially cirrhosis, hepatic encephalopathy, and alcohol-associated liver disease. Well-powered and multisite studies are needed to better understand which indications and subpopulations hold promise for FMT. At present, there is variability in the screening, processing, and administration of FMT. Some of this variability is inherent to the nature of FMT, but some of the variability could be standardized to optimize safety and efficacy. Ultimately, we may find that narrowed and donor-independent microbiome therapeutics are superior tools to provide a consistently effective result in chronic liver disease. Regulation of FMT for chronic liver disease indications in the United States will continue to require the rigid regulatory framework of other drugs, requiring an Investigational New Drug (IND) application.},
}

*Fecal Microbiota Transplantation/methods/trends/adverse effects
Humans
Gastrointestinal Microbiome
*Liver Diseases/therapy
Chronic Disease

@article {pmid41861682,
year = {2026},
author = {Ding, WL and Wang, L and Xu, BW and Lu, YN and Yue, TJ and Zhang, ZQ and Guo, FF and Han, RL and Huang, SC},
title = {Strontium chelate with Achyranthes bidentata polysaccharide as a carrier promotes bone regeneration through mediating the gut-liver-bone axis in TD chickens.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {155},
number = {},
pages = {158077},
doi = {10.1016/j.phymed.2026.158077},
pmid = {41861682},
issn = {1618-095X},
abstract = {BACKGROUND: Tibial dyschondroplasia (TD), characterized by impaired angiogenesis and abnormal chondrocyte maturation in the tibial growth plate (TGP), is a common bone disorder in commercial broilers. Strontium (Sr), a trace element with osteogenic and angiogenic properties that plays a crucial role in bone health, exhibits low bioavailability. Achyranthes bidentata polysaccharides, a major extract from Achyranthes bidentata with the function of "guiding the medicine downward", has been used to enhance drug delivery to the lower extremity meridians.

PURPOSE: This study aimed to prepare a novel Achyranthes bidentata polysaccharides-strontium (ABPS-Sr) chelate to enhance Sr bioavailability and investigate its therapeutic effects on tibial damage in TD broilers from the perspective of the gut-bone axis.

METHODS: The ABPS-Sr chelate was synthesized and optimized using response surface methodology, followed by structural characterization. A thiram-induced TD broiler model was established to evaluate the therapeutic efficacy of the ABPS-Sr chelate using qRT-PCR, Western blot, immunoprecipitation, micro-CT, histological staining, and biochemical assays. 16S rRNA sequencing and targeted and non-targeted metabolomics were employed to characterize alterations in gut microbiota, intestinal metabolites and plasma lipid metabolites. Experiments involving phosphatidylcholine (PC)-exposed broilers and fecal microbiota transplantation (FMT) in mice were performed to verify the mediate role of gut microbiota and tibia-damaging effects of PC.

RESULTS: The one-pot synthesis of ABPS-Sr chelate was optimized to achieve a yield of 27.7 %, with structural characterization confirming Sr[2+] coordination-induced conformational changes and porous architecture. Dietary supplementation with ABPS-Sr chelate significantly improved growth performance, restored tibial microstructure, and promoted vessel density in the TGP in TD broilers. Moreover, ABPS-Sr chelate promoted angiogenesis in the TGP by upregulating VEGF expression and restored osteogenic differentiation by activating the ITGB1/FAK/PI3K/AKT1 signaling pathway. Furthermore, ABPS-Sr chelate reshaped gut microbiota composition, restored intestinal barrier function, and corrected hepatic lipid metabolism disorders, particularly by reducing plasma glycerophospholipid (e.g., PC) accumulation that exerts negative effects on bone health.

CONCLUSION: This study demonstrated that ABPS-Sr chelate restores tibial injury in TD broilers by enhancing osteogenesis and angiogenesis via modulation of the gut-liver-bone axis, which provides a promising nutritional intervention strategy for improving poultry bone health.},
}

@article {pmid41850677,
year = {2026},
author = {Mi, X and Liu, R and Jiang, Z and Tang, M and Yan, J and Liu, J and Li, Y and Zheng, J and Yang, W and Gong, L and Shi, J},
title = {Gut Microbiota-Derived Propionate Governs Hepatic N2 Neutrophils in Wilson's Disease.},
journal = {Cellular and molecular gastroenterology and hepatology},
volume = {},
number = {},
pages = {101770},
doi = {10.1016/j.jcmgh.2026.101770},
pmid = {41850677},
issn = {2352-345X},
abstract = {BACKGROUND AND AIMS: Neutrophil functions play a pivotal role in hepatic pathogenesis. Our previous work has established that N2-polarized neutrophils promote hepatic fibrogenesis in Wilson's disease depends on hepatic TGF-β1 production. However, the regulators governing TGF-β1 production in orchestrating disease-associated N2 neutrophils remain elusive. In this study, we investigated the immunomodulatory effects of gut microbiota-derived short-chain fatty acids (SCFAs) on neutrophil polarization.

APPROACH AND RESULTS: We report that Akkermansia muciniphila was markedly reduced in the gut microbiota of mice with Wilson's disease, accompanied by decreased SCFA levels, especially propionate. Additionally, transplantation of fecal bacteria from wild-type mice or A. muciniphila could promote an antifibrotic effect, elevate propionate levels, reduce TGF-β1 secretion, and decrease hepatic N2 neutrophils in mice with Wilson's disease. Moreover, administration of propionate also significantly enhanced antifibrotic immunity. Mechanistically, propionate reduced the production of TGF-β1 in hepatocytes by inhibiting histone deacetylase activity, increasing the acetylation of DNAJA3 at sites K134 and K385, thus decreasing expression of DNAJA3. Consistently, gut-derived propionate inversely correlated with hepatic injury severity in Wilson's disease patients, which could be functionally mediated by TGF-β1.

CONCLUSIONS: Gut microbiota are pivotal for hepatic neutrophil polarization and liver fibrosis in Wilson's disease. Our findings suggest that therapeutic modulation of gut microbiota, SCFA profiles, and TGF-β1 production, particularly when combined with histone deacetylase inhibitors, may represent promising therapeutic approaches for Wilson's disease.},
}

@article {pmid41851729,
year = {2026},
author = {Zhu, W and Han, L and He, L and Wei, S and Li, J and Xin, L and Zhang, H and Shen, J and Song, Y and Zhou, J and Chang, CJ and Zhou, J},
title = {Parabacteroides goldsteinii-derived outer membrane vesicles alleviate acute lung injury via modulation of bile acid metabolism.},
journal = {Journal of nanobiotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12951-026-04288-3},
pmid = {41851729},
issn = {1477-3155},
support = {JSZK2019A01//Shanghai Jinshan Municipal Health Commission/ ; 20DZ2261200//Science and Technology Commission of Shanghai Municipality/ ; 20DZ2254400//Science and Technology Commission of Shanghai Municipality/ ; 82470069//National Natural Science Foundation of China/ ; 2022YFA0806200//National Key Research and Development Program of China/ ; ZD2021CY001//Shanghai Municipal Science and Technology Major Project/ ; },
abstract = {BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe clinical syndrome with limited therapeutic options. Acute lung injury (ALI) is widely used as an experimental animal model that recapitulates the key pathological features of human ARDS. Parabacteroides goldsteinii, a newly identified Gram-negative probiotic, exhibits anti-inflammatory effects in certain disease models. Gram-negative bacteria release nanoscale structures called outer membrane vesicles (OMVs), which show varying composition across species. The role of P. goldsteinii-derived OMVs (Pg-OMVs) in ALI or ARDS remains to be elucidated.

RESULT: In this study, we investigated the therapeutic potential of Pg-OMVs in a bleomycin (BLM)-induced ALI mouse model and explored their effects on pulmonary inflammation and gut microbiota composition. Compared to mice receiving BLM alone, Pg-OMV-treated mice exhibited significantly reduced inflammatory cell infiltration and lower levels of pro-inflammatory cytokines. Notably, Pg-OMV treatment significantly altered the gut microbiota composition, characterized by an increased abundance of Akkermansia muciniphila and a decreased abundance of Clostridia_bacterium. Fecal microbiota transplantation (FMT) experiments confirmed that the protective effects of Pg-OMVs were mediated via gut-lung axis. Further analysis revealed elevated cholic acid (CA) levels in the peripheral blood and bronchoalveolar lavage fluid following Pg-OMV treatment. CA was shown to suppress BLM-induced macrophage pyroptosis in the lung. Pharmacological inhibition of CA reversed the protective effects of Pg-OMVs, further confirming its pivotal role.

CONCLUSIONS: In summary, Pg-OMVs increased the abundance of Akkermansia muciniphila while decreasing the abundance of Clostridia_bacterium in the gut, elevated systemic CA levels, and suppressed macrophage pyroptosis via inhibition of the NF-κB pathway, thereby attenuating pulmonary inflammation and ultimately alleviating ALI. These findings highlight a novel therapeutic strategy for the treatment of ALI or ARDS by targeting the gut-lung axis.},
}

@article {pmid41852385,
year = {2025},
author = {Ataei, P and Kalantari, H and Bodnar, TS and Turner, RJ},
title = {The gut-brain connection: microbes' influence on mental health and psychological disorders.},
journal = {Frontiers in microbiomes},
volume = {4},
number = {},
pages = {1701608},
pmid = {41852385},
issn = {2813-4338},
abstract = {The human gut microbiome has emerged as a pivotal modulator of brain function and mental health, acting through intricate bidirectional communication along the gut-brain axis. Mounting evidence suggests that microbial communities influence neurodevelopment, neurotransmission, and behavior via pathways involving the vagus nerve, immune signaling, and microbiota-derived metabolites such as short-chain fatty acids and neurotransmitter precursors. This review critically examines the mechanistic underpinnings of microbiota-brain communication and evaluates current findings linking dysbiosis to psychiatric conditions, including depression, anxiety, schizophrenia, autism spectrum disorder, and bipolar disorder. In addition, it assesses the therapeutic potential of microbiome-targeted interventions-such as probiotics, fecal microbiota transplantation (FMT), and precision dietary modulation-in ameliorating neuropsychiatric symptoms. While the field holds considerable promise, limitations, including correlational study designs, small sample sizes, and a lack of standardized methodologies, underscore the need for rigorous, large-scale clinical trials. A deeper understanding of host-microbe interactions may catalyze a paradigm shift in psychiatric treatment, paving the way for novel, personalized microbiome-based therapeutics.},
}

@article {pmid41852399,
year = {2025},
author = {Tillotson, G},
title = {Editorial: Live Biotherapeutic Products: where are we?.},
journal = {Frontiers in microbiomes},
volume = {4},
number = {},
pages = {1664282},
pmid = {41852399},
issn = {2813-4338},
}

@article {pmid41852409,
year = {2025},
author = {Bailey, A and Leuther, KK and Robinson, LA},
title = {The microbiome and lung cancer: microbial effects on host immune responses and treatment outcomes.},
journal = {Frontiers in microbiomes},
volume = {4},
number = {},
pages = {1606551},
pmid = {41852409},
issn = {2813-4338},
abstract = {The human microbiome plays a critical role in shaping physiological processes, immune system function, metabolism, and disease development. Recent research has highlighted the microbiome's profound cancer impact, particularly on lung cancer. This review explores how microbial communities in lung and gut influence tumor progression, immune responses, and treatment outcomes as well as describing the interactions between the microbiome and the host immune system in modulating the efficacy of cancer therapies. Emerging evidence from preclinical and clinical studies investigating the role of the lung and gut microbiome in lung cancer focus on alterations in the microbiota that influence the tumor microenvironment, modulate immune responses, and potentially enhance/hinder treatment effectiveness such as chemotherapy, targeted therapies, and immunotherapy. Microbial diversity plays a significant role in immune regulation, and specific microbial species may activate/suppress immune cells such as T-cells, dendritic cells, and macrophages. Furthermore, this review examines the therapeutic implications of microbiome modulation, including the use of probiotics, antibiotics, and fecal microbiota transplantation in enhancing cancer therapies. Alterations in the lung and gut microbiome and their interaction in the recently described gut-lung axis with its bidirectional communication significantly influence the tumor microenvironment and systemic immune responses. These findings suggest that microbial diversity can regulate immune functions, with specific species capable of activating or suppressing immune cell activity. Furthermore, microbiome-targeted interventions show potential in improving the effectiveness of treatments including chemotherapy, targeted therapies, and immunotherapy, underscoring the importance of the microbiome as a key factor in lung cancer pathogenesis and treatment.},
}

@article {pmid41852427,
year = {2025},
author = {Al-Kuwari, A and Al-Karbi, H and Al-Khuzaei, A and Baroudi, D and Bendriss, G},
title = {Beyond antibiotics: leveraging microbiome diversity to combat antimicrobial resistance.},
journal = {Frontiers in microbiomes},
volume = {4},
number = {},
pages = {1618175},
pmid = {41852427},
issn = {2813-4338},
abstract = {The best way to fight harmful microbes may not lie in new antibiotics, but rather in leveraging the power of microbes themselves. Antimicrobial resistance (AMR) is a growing global concern, where the overuse of antibiotics has led to the emergence of resistant strains. This paper explores the potential of increasing diversity in gut microbiomes as natural approaches to fight AMR. The promotion microbial diversity is proposed as a promising strategy to reduce dependency on antibiotics by fostering a resilient microbial community. Strategies are discussed to address the loss of diversity caused by antibiotics including diet, probiotics, fecal transplants (FMT) and fermentation of animal/plant products. Preliminary findings from an experiment with camel milk fermentation suggest that fermentation can increase microbial diversity, potentially affecting resistance to common antibiotics such as tetracycline, streptomycin, penicillin, and chloramphenicol, and enhancing microbiome resilience, allowing it to naturally resist pathogens without additional antibiotic use. The results highlight both the benefits and potential risks fermented products. Additionally, FMT, naturally occurring in the animal world, is a promising method to restore microbiome balance and mitigating the impact of AMR. A mechanistic model is discussed to underscore the importance of maintaining microbial balance as an effective strategy for mitigating AMR and promoting long-term health. Further research are needed to better understand the mechanisms behind these changes and their implications for public health. This perspective paper calls for a shift in the approach to AMR, advocating for microbiome-based solutions as a sustainable alternative to traditional pharmaceutical interventions.},
}