@article {pmid41284175,
year = {2025},
author = {Olesen, RH and Larsen, EB and Rubak, T and Baunwall, SMD and Paaske, SE and Gregersen, M and Erikstrup, C and Olsen, K and Dahlerup, JF and Kjaer, TK and Krogh, CB and Ehlers, LH and Hvas, CL},
title = {Increasing patient access to faecal microbiota transplantation with remote delivery: a cost analysis of outpatient versus home-based treatment.},
journal = {Health economics review},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13561-025-00706-8},
pmid = {41284175},
issn = {2191-1991},
support = {NNF22OC0074080//Novo Nordisk Foundation/ ; },
abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) is used in less than 10% of the patients in Europe who meet the indication. Encapsulated FMT allows increased use for CDI because capsules can be safely shipped to local healthcare facilities and administered orally to patients without use of e.g. colonoscopy. The aim of this study was to calculate and compare the costs of alternative ways of delivering encapsulated FMT to patients with CDI in Denmark, including outpatient treatment at a specialised FMT centre, outpatient treatment at local hospitals including remote delivery to the Faroe Islands, and home-based care.

METHODS: Applying a healthcare perspective, we used an activity-based costing approach, combining data from a pragmatic clinical randomised trial with the best available literature and expert input. Only relevant costs were included. The main outcome was the average cost of delivering outpatient, encapsulated FMT treatment at an FMT centre, at a local hospital, or in the patient's home, only including additional costs related to delivery. An 8-week time horizon was applied for the analysis. Probabilistic and deterministic sensitivity analyses were applied to evaluate decision uncertainty and the robustness of the results.

RESULTS: In a pragmatic randomised trial including 217 patients with CDI, 135 patients received FMT. Analysing relevant costs in a base case analysis, local outpatient treatment (€145) was cost-saving compared with both treatment at the FMT centre (€209) and home-based treatment (€353). These differences remained robust across sensitivity analyses, including those accounting for patients' time costs. In the Faroe Islands case, shipment to remote locations added an average cost of €54 per FMT to the cost for the local outpatient treatment.

CONCLUSION: Capsule-based FMT treatment has made it clinically and economically feasible to administer FMT in contextual settings outside of specialised hospitals. Our findings highlight the importance of local hospital-based treatment for increasing patient access to FMT, the ability to ship FMT to remote locations lacking a FMT centre, and the option of home-based treatment for a selected group of patients who may not tolerate transport to hospital.},
}

@article {pmid41282240,
year = {2025},
author = {Gancz, A and Zhang, G and McMillan, A and Dougherty, M and McGill, S and Gulati, A and Baker, E and Theriot, C},
title = {Successful Fecal Microbiota Transplants in Post-antibiotic Treated Recurrent Clostridioides difficile Patients Induce Acylcarnitine and Sphingolipid Lipidomic Shifts.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7888346/v1},
pmid = {41282240},
issn = {2693-5015},
abstract = {Clostridioides difficile infection (CDI) is an urgent public health threat in the United States, resulting on an annual basis in over half a million cases, more than 29,000 deaths, and $4.8 billion in healthcare costs. While fecal microbiota transplants (FMTs) have proven more effective than standard-of-care antibiotics in resolving recurrent CDI (rCDI), their inherent risks underscore the need for advancements in regulated alternative therapies such as live biotherapeutic products (LBPs). The development of effective LBPs, however, is contingent upon better understanding the biological mechanisms underlying FMT efficacy. Building on our previously published untargeted metabolomic study which identified lipids as major explanatory factors associated with successful FMTs, we assessed additional lipid species using an instrumental platform coupling liquid chromatography, ion mobility spectrometry, collision induced dissociation, and mass spectrometry (LC-IMS-CID-MS) techniques. This platform and data analysis workflow enable the evaluation of >850 unique lipid species across 26 classes. Here, we confidently identified 397 lipids in the stools of 15 rCDI patients at pre- and post-FMT (2 week, 2 month, and 6 month) time points. Statistical evaluations of the lipidomic data illustrated that FMT-administration drastically reshapes the lipidome (adonis test, R [2] =0.11999, Pr(>F) <0.001), including 96 specific lipid species across 18 lipid classes (mixed effects modeling, BH correction, p < 0.05). In particular, we noted that medium and long-chain acylcarnitines decreased following FMT administration, while very long-chain acylcarnitines were elevated in post-FMT samples. Additionally, we observed assayed sphingolipids to be elevated pre-FMT with the exception of trihydroxy ceramides, which were highly upregulated post-FMT. These lipidomic alterations suggest that FMT administration may influence intestinal barrier integrity, inflammatory signaling, or apoptosis pathways. Interestingly, there was a strong co-occurrence of medium and long-chain acylcarnitines with Enterobacteriaceae, a bacterial family that has been demonstrated to utilize carnitine for growth. These findings highlight the critical role of the lipidome in patient susceptibility to rCDI and suggest the interactions between microbiota and lipids pre- and post-FMT as targets for developing next-generation LBPs.},
}

@article {pmid41282164,
year = {2025},
author = {Gavini, C and Raux, L and Labouèbe, G and Gornick, E and Hugh, SM and Elshareif, N and Calcutt, N and Summa, PD and Gorostidi, F and Vonaesch, P and Mansuy-Aubert, V},
title = {Dietary Fiber Improves Somatosensory Function in Western Diet-Fed Mice by Remodeling Adipose Immune Cells via FFAR2 Signaling.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7868021/v1},
pmid = {41282164},
issn = {2693-5015},
abstract = {Westernized diets (WDs)-high in fat and sugar and low in fiber-produce somatosensory deficits, chronic pain, and neuropathy, yet the mechanisms linking diet to peripheral nervous system (PNS) pathology remain incompletely defined. Emerging evidence implicates gut-derived metabolites in sensory homeostasis; for example, fecal microbiota transplantation (FMT) from lean donors to WD fed mice reduces hypersensitivity and attenuates PNS inflammation, although FMT outcomes are variable. We therefore tested whether targeted modulation of the gut microbiota with fermentable complex carbohydrates could reproducibly improve somatosensory function in WD-fed mice. Using an integrated pipeline-behavioral and physiological assays, peripheral nerve electrophysiology, and molecular and immune profiling-we show that short-chain fatty acids (SCFAs) generated by fermentation remodel adipose tissue depots and act via the SCFA receptor FFAR2 (GPR43) to ameliorate sensory deficits. These findings identify a microbiota-SCFA-FFAR2 axis that couples dietary fiber to PNS function and provide a tractable alternative to FMT for mitigating WD-associated sensory neuropathy.},
}

@article {pmid41282140,
year = {2025},
author = {Gascoigne, N and Wojciech, L and Prasad, M and Brzostek, J and Rybakin, V and Hoerter, J and Hou, B and Tung, D and Chua, YL and Ampudia, J and Rai, A and Chodaczek, G and Fu, G and Pettersson, S},
title = {The role of Themis in development of type 2 diabetes.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7943370/v1},
pmid = {41282140},
issn = {2693-5015},
abstract = {Type 2 diabetes (T2D) is a complex metabolic disorder driven by chronic inflammation and immune dysregulation, particularly within adipose tissue. This study investigates the role of the T cell-specific protein Themis in modulating immune-metabolic interactions that contribute to T2D pathogenesis. Using high-fat diet (HFD)-induced obesity models, we demonstrate that Themis -deficient (KO) mice exhibit accelerated weight gain, glucose intolerance, and insulin resistance compared to wild-type (WT) controls. These metabolic abnormalities are linked to functional alterations in the CD8[+] T cell compartment, including site-specific clonal expansion and reshaping of the T cell receptor (TCR) repertoire within adipose tissue, suggesting antigen-driven activation. Additionally, Themis deficiency leads to significant shifts in gut microbiome composition, characterized by reduced diversity and increased abundance of Firmicutes , particularly Clostridium species. However, fecal microbiota transplantation from Themis KO mice into germ-free WT hosts failed to recapitulate the full T2D phenotype, underscoring the dominant role of intrinsic immune dysfunction over microbial dysbiosis. These findings highlight a synergistic interplay between adaptive immunity and the microbiome in shaping metabolic outcomes and suggest that T cells play a central role in responses that influence T2D progression. Our data advocate for a more integrated approach to T2D research, incorporating genetic, immunological, and microbial factors.},
}

@article {pmid41281485,
year = {2025},
author = {Demirli Atici, S},
title = {Innovative insights into gut microbiota modulation in colorectal cancer: From microbial dysbiosis to therapeutic strategies.},
journal = {World journal of gastrointestinal oncology},
volume = {17},
number = {11},
pages = {108747},
pmid = {41281485},
issn = {1948-5204},
abstract = {Colorectal cancer (CRC) is increasingly recognized as a multifactorial disease influenced by hereditary, environmental, and microbial factors. This article explores recent insights into the role of gut microbiota dysbiosis in CRC pathogenesis and progression. Key differences in microbial composition, characterized by enrichment of pro-carcinogenic species such as Fusobacterium nucleatum and Bacteroides fragilis and depletion of beneficial commensals like Faecalibacterium prausnitzii, have been identified alongside changes in microbial metabolites such as short-chain fatty acids and secondary bile acids. We discuss immune system modulation by the microbiota, formation of bacterial biofilms, and the activation of host pathways such as the urea cycle during tumorigenesis. Special attention is given to therapeutic innovations, including microbiota-informed precision modelling, synthetic biology-based engineered probiotics, and evolving alternatives to fecal microbiota transplantation. These integrative strategies represent promising tools in the era of personalized oncology for CRC.},
}

@article {pmid41281468,
year = {2025},
author = {Rijkers, GT and Langcauon, Y and van Leersum, P and Popović, L and van Overveld, FJ},
title = {Role of microbiota in the outcome of immune checkpoint inhibition therapy of cancer.},
journal = {Exploration of targeted anti-tumor therapy},
volume = {6},
number = {},
pages = {1002348},
pmid = {41281468},
issn = {2692-3114},
abstract = {The realization that the composition and functionality of gut microbiota have an impact on the outcome of immune checkpoint inhibition (ICI) therapy of cancer has initiated research into the potential of microbiota management as adjunctive therapy. Fecal microbiota transplantation can improve the outcome of ICI, but for optimal donor selection, safety, and large-scale implementation, there remain bottlenecks. Alternative strategies, such as the use of selected bacterial species, require fundamental knowledge of the underlying mechanisms governing the interaction between (intestinal) microbiota and the immune system. Gut microbiota also appears to be able to colonize the tumor microenvironment. Some bacterial species directly or indirectly promote tumor growth. Other defined species have tumoricidal properties. These findings and insights are now being used to further optimize the functionality of the immune system and shape the tumor microenvironment in order to improve the outcome of ICI.},
}

@article {pmid41280983,
year = {2025},
author = {Nadeem, O and Imran, MS and Siddique, N},
title = {Recurrent Clostridium difficile Infections in a Patient With Ulcerative Colitis: A Case Report.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e95130},
pmid = {41280983},
issn = {2168-8184},
abstract = {Clostridium difficile infection (CDI) poses a substantial clinical challenge, especially in patients with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). Patients with UC are at greater risk of CDI and tend to experience a more severe disease course and higher rates of recurrence than the general population. We report a case of an elderly man in his early 90s with a long-standing history of UC treated with mesalazine, who had a prior hospitalization for hyponatremia and a history of CDI. During his most recent four-month hospitalization, he developed three separate episodes of CDI, confirmed by stool PCR and toxin assays. Despite treatment with vancomycin, metronidazole, and fidaxomicin in succession, he experienced recurrent episodes of CDI that ultimately progressed to septic shock and death. This case highlights the nature of recurrent CDI in this patient population and the complexity and increased morbidity associated with its management in elderly patients with UC. It underscores the importance of careful evaluation of underlying risk factors, judicious antibiotic use, and consideration of alternative treatment modalities, such as faecal microbiota transplantation (FMT), for the prevention of recurrent CDI.},
}

@article {pmid41280921,
year = {2025},
author = {Li, X and Yuan, Q and Huang, H and Wang, L},
title = {Gut microbiota in irritable bowel syndrome: a narrative review of mechanisms and microbiome-based therapies.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1695321},
pmid = {41280921},
issn = {1664-3224},
mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Dysbiosis/therapy ; Animals ; Prebiotics/administration & dosage ; },
abstract = {Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, and its pathogenesis remains unclear. Dysbiosis of the gut microbiota is associated with IBS. The gut microbiota may modulate IBS symptoms via the epithelial barrier, mucosal immunity, microbial metabolites (e.g., short-chain fatty acids and bile acids), and gut-brain signaling. Currently, dietary approaches, probiotics, prebiotics, rifaximin, and fecal microbiota transplantation show variable benefit; effects are strain-/context-dependent and evidence certainty varies, with adverse-event reporting inconsistent. This narrative review takes a subtype-aware, mechanism-first perspective to summarize microbiota functions, symptom links, and intervention evidence with safety considerations. This review offers new perspectives and insights for precision treatment and microbiome research in IBS.},
}

Humans
*Irritable Bowel Syndrome/therapy/microbiology/immunology
*Gastrointestinal Microbiome/immunology
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Dysbiosis/therapy
Animals
Prebiotics/administration & dosage

@article {pmid41280320,
year = {2025},
author = {Shackelford, BB and Kedir, K and Babiker, A and Sintayehu, B and Negash, AA and Abdissa, A and Taye, WA and Beyene, E and Woodworth, MH and Hennink, MM},
title = {Knowledge and Acceptability of Fecal Microbiota Transplantation Among Patients, Caregivers, and Health Care Providers in Ethiopia.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf676},
pmid = {41280320},
issn = {2328-8957},
abstract = {BACKGROUND: Malnutrition and antimicrobial-resistant infections are major causes of morbidity and mortality in low-income countries. These conditions have been associated with the gut microbiome, although little is known about the acceptability of microbiota therapies such as fecal microbiota transplantation (FMT). We explored the acceptability of FMT among health care providers (HCPs) and patients in Addis Ababa, Ethiopia.

METHODS: In this qualitative study, we purposively sampled patients with bacterial infections and acute malnutrition, caregivers, and HCPs at two hospitals. Eight focus group discussions were held. Amharic and English discussion guides covered knowledge of FMT and perceived barriers or facilitators for uptake. Data were transcribed and translated into English when necessary. MAXQDA software was used for a thematic analysis, with trained researchers closely reading transcripts to identify issues, develop a codebook, iteratively code data, and assess intercoder agreement. Description, comparison, and categorization were conducted to discern core themes, and validity checks ensured that findings were grounded in the data.

RESULTS: HCPs indicated a general willingness to prescribe FMT, provided that there was sufficient evidence supporting its efficacy and safety and they were confident on patient adherence. Patient acceptability of FMT was categorized along a continuum from those who were unconvinced, persuadable, amenable, and accepting of salvage treatment.

CONCLUSIONS: FMT may be acceptable for HCPs and patients in Addis Ababa, although interventions are needed to enhance acceptance among some groups, such as marketing it as standard medication, obtaining endorsement by religious leaders, providing multiple formulations, and/or providing thoughtful health communication.},
}

@article {pmid41280275,
year = {2026},
author = {Qi, X and Zhang, Y and Sun, Z and Wang, G and Ling, F},
title = {A simplified synthetic microbial community enhances resistance of crucian carp (Carassius auratus) to Aeromonas hydrophila infection through host immune activation.},
journal = {Synthetic and systems biotechnology},
volume = {11},
number = {},
pages = {407-418},
pmid = {41280275},
issn = {2405-805X},
abstract = {Bacterial diseases represent a major bottleneck in the sustainable development of aquaculture. The gut microbiota plays a vital role in host growth and health, including the enhancement of disease resistance. Although substantial progress has been made in elucidating the mechanisms of disease resistance in fish, the precise role of the gut microbiota in enhancing pathogen resistance in aquatic animals remains poorly understood. In this study, crucian carp (Carassius auratus) were used as a model to investigate the role of intestinal microbiota in modulating resistance to Aeromonas hydrophila. Individual crucian carp exhibited distinct clinical phenotypes following A. hydrophila infection. Specifically, significant differences were observed in the composition of the intestinal microbiota between fish displaying mild symptoms and those exhibiting severe phenotypic manifestations (α diversity: p < 0.01; β diversity: p = 0.001). Fecal microbiota transplantation (FMT) experiments demonstrated that fish with mild symptoms conferred enhanced resistance to A. hydrophila when their intestinal contents were transplanted into other individuals (p = 0.006). Further microbial analysis identified Cetobacterium (p = 0.013), Paraclostridium (p < 0.01), and Pseudomonas (p < 0.01) as key differential taxa. A simplified microbial community comprising these three strains was subsequently constructed. Feeding experiments confirmed that administration of this community significantly improved host resistance to A. hydrophila (p < 0.05) by activating intestinal immune responses and reinforcing the gut barrier. Overall, our findings underscore the potential of the microbial community as a novel strategy for disease prevention and control in aquaculture, providing a theoretical foundation for the development of microbiome-based therapies in fish health management.},
}

@article {pmid41278627,
year = {2025},
author = {Pandey, S and Abu, YF and Singh, P and Roy, S},
title = {Cross-Fostering with control dams rescues Gut Dysbiosis and Chromatin-associated Transcriptional Changes in Offspring of Opioid-Exposed Dams.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.07.687278},
pmid = {41278627},
issn = {2692-8205},
abstract = {Prenatal opioid exposure disrupts gut homeostasis and causes gastrointestinal complications in offspring, but the mechanisms remain unclear. Here using a murine model of prenatal hydromorphone exposure, we examined gut microbiota, intestinal injury, transcriptomic signatures, and chromatin accessibility. Exposed pups displayed marked dysbiosis, epithelial damage, and upregulation of inflammatory gene programs accompanied by relaxed ileal chromatin. Cross-fostering to opioid-naïve dams restored microbial diversity, reestablished metabolite-producing taxa, and reversed injury-associated transcriptional and chromatin changes. Fecal microbiota transplantation from exposed dams recapitulated intestinal injury, indicating a microbiome-driven mechanism. These findings reveal a novel gut-microbiome-epigenome axis underlying opioid-induced injury and highlight early microbial intervention as a potential strategy to mitigate developmental harm.},
}

@article {pmid41278477,
year = {2025},
author = {Chang, L and Liu, Y and Li, H and Yan, J and Wu, W and Chen, N and Ma, C and Zhao, X and Chen, J and Zhang, J},
title = {Gut microbiome and its metabolites in liver cirrhosis: mechanisms and clinical implications.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1717696},
pmid = {41278477},
issn = {2235-2988},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Cirrhosis/microbiology/metabolism/pathology ; Dysbiosis/microbiology ; Bile Acids and Salts/metabolism ; Fatty Acids, Volatile/metabolism ; Animals ; },
abstract = {Cirrhosis remains a significant global health burden, causing approximately 1.4-1.5 million deaths each year and contributing to nearly 46 million disability-adjusted life years (DALYs) worldwide. Increasing evidence identifies the gut-liver axis as a central driver of disease progression, wherein intestinal dysbiosis, barrier disruption, and microbe-derived metabolites collectively exacerbate inflammation, fibrogenesis, and related complications. Across more than 40 recent studies, gut microbial α-diversity declined by 30-60%, and over 80% reported a marked depletion of short-chain fatty acid (SCFA)-producing taxa, particularly Lachnospiraceae and Ruminococcaceae. Meta-analyses indicate that fecal butyrate levels decrease by 40-70%, accompanied by a two- to fourfold increase in endotoxin concentrations. Bile acid profiling demonstrates an approximately 50% reduction in secondary bile acids and significant suppression of FXR/TGR5 signaling, whereas tryptophan metabolism shifts toward the kynurenine pathway, weakening epithelial defense and exacerbating portal hypertension. Clinically, dysbiosis and microbial translocation are associated with higher MELD scores, and patients in the lowest quartile of microbial diversity have a threefold increased risk of hepatic encephalopathy or spontaneous bacterial peritonitis. Microbiome-targeted interventions-including lactulose, rifaximin, probiotics or synbiotics, fecal microbiota transplantation, and bile acid modulators-restore community balance in 70-85% of clinical trials, although efficacy and safety vary by etiology and baseline microbiota composition. Integrated microbiome-metabolome models achieve areas under the curve (AUCs) of 0.82-0.90 for noninvasive classification and early detection of cirrhosis. Collectively, these findings underscore reproducible, quantitative microbiome-metabolite alterations and outline a roadmap for microbiome-informed precision care that connects mechanistic insight with clinical application, emphasizing the need for longitudinal and multi-ethnic validation.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Liver Cirrhosis/microbiology/metabolism/pathology
Dysbiosis/microbiology
Bile Acids and Salts/metabolism
Fatty Acids, Volatile/metabolism
Animals

@article {pmid41278154,
year = {2025},
author = {Zheng, L and Duan, SL and Wang, K},
title = {Research progress concerning the involvement of the intestinal microbiota in the occurrence and development of inflammatory bowel disease.},
journal = {World journal of gastroenterology},
volume = {31},
number = {42},
pages = {113170},
pmid = {41278154},
issn = {2219-2840},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology/genetics ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Intestinal Mucosa/microbiology/immunology/pathology ; *Crohn Disease/microbiology/therapy/immunology ; *Colitis, Ulcerative/microbiology/therapy/immunology ; Genetic Predisposition to Disease ; Dysbiosis/microbiology/immunology/therapy ; *Inflammatory Bowel Diseases/microbiology/therapy ; Metagenomics ; Animals ; Metabolomics ; Immunity, Mucosal ; },
abstract = {Inflammatory bowel disease (IBD), a chronic disorder characterized by intestinal inflammation and mucosal damage, includes mainly Crohn's disease and ulcerative colitis. However, the cause of its onset remains unclear. The pathogenesis of IBD is closely related to host genetic susceptibility, disorders of the intestinal flora, damage to the intestinal mucosal barrier, and abnormal intestinal mucosal immunity. On the basis of the progress in research on the structure of the intestinal microbiota involved in IBD, the influence of genetics on the intestinal barrier and intestinal microbiota; the metagenomics, metatranscriptomics, and metabolomics of the intestinal microbiota involved in IBD; and treatments such as probiotics and fecal microbiota transplantation are important for the future treatment of IBD and the development of drugs for effective treatment.},
}

Humans
*Gastrointestinal Microbiome/immunology/genetics
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Intestinal Mucosa/microbiology/immunology/pathology
*Crohn Disease/microbiology/therapy/immunology
*Colitis, Ulcerative/microbiology/therapy/immunology
Genetic Predisposition to Disease
Dysbiosis/microbiology/immunology/therapy
*Inflammatory Bowel Diseases/microbiology/therapy
Metagenomics
Animals
Metabolomics
Immunity, Mucosal

@article {pmid41278045,
year = {2025},
author = {Hamza Saeed, M and Qamar, S and Ishtiaq, A and Umaira Khan, Q and Atta, A and Atta, M and Ishtiaq, H and Khan, M and Saeed, MR and Iqbal, A},
title = {Retraction: Fecal Microbiota Transplantation (FMT) in Clostridium difficile Infection: A Paradigm Shift in Gastrointestinal Microbiome Modulation.},
journal = {Cureus},
volume = {17},
number = {11},
pages = {r206},
doi = {10.7759/cureus.r206},
pmid = {41278045},
issn = {2168-8184},
abstract = {[This retracts the article DOI: 10.7759/cureus.85054.].},
}

@article {pmid41277972,
year = {2025},
author = {Ye, N and Song, X and Yu, J and Bao, X and Ye, M and Jiang, L},
title = {Effects of gut microbiota interventions on patients with schizophrenia: a systematic review and meta-analysis.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1681559},
pmid = {41277972},
issn = {1664-302X},
abstract = {INTRODUCTION: Schizophrenia (SCH) is a chronic psychiatric disorder characterized by disturbances in thought, emotion, perception, and behavior. Although gut microbiota interventions (e.g., probiotics, prebiotics, synbiotics, dietary modifications and fecal microbiota transplantation) have been widely applied in the treatment of SCH, the most effective intervention strategy remains uncertain.

METHODS: By searching four databases, only randomized controlled trials (RCTs) were included to examine the impacts of gut microbiota interventions on SCH. The Cochrane risk-of-bias tool for randomized trials (RoB 2.0) was employed to assess the methodological quality of the included studies, RevMan5.4 was used for the meta-analysis, Stata 18 was used for sensitivity analysis, Engauge Digitizer was used to convert pictures to numbers and GRADEPro3.6 was used to grade the evidence quality.

RESULTS: This study incorporated RCTs published from the earliest records up to December 2024. A total of 10 RCTs, encompassing 585 participants, were analyzed. The meta-analysis demonstrated that interventions primarily utilizing probiotics to modulate gut microbiota significantly lowered the total Positive and Negative Syndrome Scale (PANSS) scores among patients (p = 0.001). Furthermore, substantial improvements were observed across multiple metabolic parameters: fasting blood sugar, triglycerides, total cholesterol, homeostasis model assessment of insulin resistance, and quantitative insulin sensitivity check index (all p < 0.05). While no significant effects were observed on high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, body weight, body mass index, and insulin.

CONCLUSION: This meta-analysis suggests that auxiliary probiotic interventions hold promise as an adjunctive therapy for schizophrenia, potentially yielding benefits in psychopathological, metabolic, and physiological domains. However, the current evidence remains inconclusive due to the limited number of studies, small sample sizes, and methodological variations. Firm therapeutic recommendations cannot be made at this time. The findings underscore the need for more robust, large-scale, and rigorously designed randomized controlled trials to definitively establish the efficacy and optimal protocols of auxiliary probiotic supplementation for SCH.

https://www.crd.york.ac.uk/PROSPERO, CRD 420250652507.},
}

@article {pmid41277959,
year = {2025},
author = {Zhang, S and Li, J and Li, L and Yuan, X},
title = {Gut microbiota on cardiovascular diseases-a mini review on current evidence.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1690411},
pmid = {41277959},
issn = {1664-302X},
abstract = {The gut microbiome has emerged as a critical modulator of cardiovascular disease (CVD) risk, offering a novel frontier for therapeutic intervention. This mini-review synthesizes current evidence on how probiotic-like bacteria and their metabolites mediate protective physiological mechanisms against CVD. Drawing from both animal models and human clinical trials, we elucidate the biological pathways, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acid metabolism, through which the gut microbiota influences hypertension, atherosclerosis, and heart failure. Furthermore, we examine microbiota-based strategies such as dietary modification, fecal microbiota transplantation (FMT), and pharmacological agents aimed at restoring microbial homeostasis. Despite promising mechanistic insights, human trials have yet to consistently demonstrate significant clinical benefits in reversing CVD outcomes via gut microbiota modulation. This review underscores the necessity of moving from correlation to causation, highlighting current limitations and future prospects for leveraging gut microbiome research in the development of personalized, effective therapeutic strategies for cardiovascular diseases.},
}

@article {pmid41277418,
year = {2025},
author = {Guggeis, MA and Andreani, NA and López-Agudelo, VA and Tran, F and Kadibalban, AS and Moors, KA and Marinos, G and Saboukh, A and Harris, D and Falk-Paulsen, M and Weber-Stiehl, S and Järke, L and Sommer, F and Welz, L and Bang, C and Franke, A and Chung, CJ and Bronowski, C and Schuchardt, S and Künzel, S and Aden, K and Schreiber, S and Kaleta, C and Baines, JF and Rosenstiel, P},
title = {Cross-species engraftment biases and metabolic divergence in gnotobiotic mice humanized with ulcerative colitis microbiota.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2581445},
doi = {10.1080/19490976.2025.2581445},
pmid = {41277418},
issn = {1949-0984},
mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/microbiology/therapy/metabolism ; *Fecal Microbiota Transplantation ; Germ-Free Life ; Mice, Inbred C57BL ; Mice ; Bacteria/classification/genetics/isolation & purification/metabolism ; Disease Models, Animal ; Male ; Female ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/microbiology ; Fungi/classification/genetics/isolation & purification ; Middle Aged ; },
abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the human colon. Dysbiotic gut microbiota play a central role in its pathogenesis, and alterations in microbial composition and function are closely linked to disease activity. Humanized gnotobiotic mice are increasingly used to study how dysbiotic, human-derived microbial communities shape intestinal inflammation. However, the fidelity of microbiota engraftment and its impact on host physiology and metabolism remain incompletely understood. In this study, we performed a multiomics analysis following fecal microbiota transfer (FMT) from eight patients with active UC into germ-free C57BL/6N mice (five mice per donor). The mice were monitored over three weeks. Longitudinal analysis of microbial communities was performed using 16S rRNA (bacteria) and ITS2 (fungi) amplicon sequencing. Microbial metabolic flux was inferred via genome-scale metabolic modeling, and plasma metabolites were assessed by targeted metabolomics. We observed donor-specific physiological changes in recipient mice, including variations in body weight and adipose tissue. Spontaneous colonic inflammation occurred in one group and was subsequently linked to unintended transfer of Clostridioides difficile, which was previously clinically unrecognised in the donor. While bacterial engraftment overall was generally donor-specific and stable across mice, fungal taxa were transferred inconsistently and at low abundance. Despite similar overall plasma metabolomic profiles, select metabolites, including 3-indoleacetic acid, were differentially associated with specific microbial taxa. Moreover, metabolic modeling revealed disrupted metabolic exchange networks in the mouse microbiota compared to the original human donor communities. In conclusion, while human FMT into germ-free mice reliably transmits bacterial features, it introduces metabolic alterations and fails to fully reproduce the fungal microbiome. These findings underscore the need for cautious interpretation of microbiota-driven effects in gnotobiotic models and highlight the limitations of current approaches in replicating the full complexity of human gut ecosystems.},
}

Animals
Humans
*Gastrointestinal Microbiome
*Colitis, Ulcerative/microbiology/therapy/metabolism
*Fecal Microbiota Transplantation
Germ-Free Life
Mice, Inbred C57BL
Mice
Bacteria/classification/genetics/isolation & purification/metabolism
Disease Models, Animal
Male
Female
Feces/microbiology
RNA, Ribosomal, 16S/genetics
Dysbiosis/microbiology
Fungi/classification/genetics/isolation & purification
Middle Aged

@article {pmid41277357,
year = {2025},
author = {Zheng, X and Jiang, Y and Wang, W and Sun, K and Zhou, L and Zhang, Y and Cui, J and Yu, H and Dong, W and Yan, B},
title = {Asiatic Acid Alleviates Ulcerative Colitis Through a Gut Microbiota-Driven cAMP/PKA/NF-κB Pathway: γ-Glutamyltyrosine Is a Crucial Player.},
journal = {Phytotherapy research : PTR},
volume = {},
number = {},
pages = {},
doi = {10.1002/ptr.70132},
pmid = {41277357},
issn = {1099-1573},
support = {82304807//National Natural Science Foundation of China/ ; BK20220299//Natural Science Foundation of Jiangsu Province/ ; Syhky202307//Clinical Pharmaceutical Research Foundation of Jiangsu Hengrui Medicine/ ; JLY2021052//Clinical Medical Science and Technology Development Foundation of Jiangsu University/ ; KS2203//Science and Technology Project of Kunshan/ ; KSF202139//Science and Technology Project of Kunshan/ ; },
abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by recurrent flare-ups and limited effectiveness of available drug therapies. Asiatic acid (AA), a triterpenoid compound extracted from Centella asiatica, has shown promising pharmacological activities and therapeutic potential in several inflammation-related diseases. However, AA's efficacy in treating UC and its precise mechanisms of action remain to be fully explored. This study aimed to provide a comprehensive assessment of AA's therapeutic effects on UC and to investigate its underlying mechanisms, with a focus on gut microbiota interactions. In our study, a dextran sulfate sodium-induced UC mouse model was used to evaluate AA's therapeutic potential and explore its impact on gut microbiota composition and function. We further used an antibiotic cocktail and fecal microbiota transplantation assays to substantiate the role of gut microbiota in AA's mechanisms of action. A metabolomic analysis was also conducted to identify key metabolic pathways and gut microbiota-derived metabolites involved in AA's effects. Our findings demonstrated that AA significantly alleviates symptoms of UC, including reducing weight loss, slowing disease progression, mitigating colonic inflammation, and restoring immune balance. Mechanistically, the beneficial effects of AA were strongly linked to alterations in the gut microbiota and its metabolites, particularly γ-glutamyltyrosine. This metabolite was found to regulate the cyclic adenosine monophosphate/protein kinase A/nuclear factor kappa-B signaling pathway, which plays a crucial role in inflammatory responses. Overall, these findings strongly suggest that AA holds promise as a therapeutic agent for UC by modulating the gut microbiota and influencing critical inflammatory pathways.},
}

@article {pmid41276714,
year = {2025},
author = {Mustafa, MA and Vadia, N and Varma, P and Al-Shaker, H and Mohanty, B and Dhyani, A and Kaur, I and Chauhan, AS and Garg, G},
title = {The Gut-Brain Axis in Alzheimer's Disease: Exploring Microbial Influences and Therapeutic Strategies.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {151},
pmid = {41276714},
issn = {1559-1182},
mesh = {*Alzheimer Disease/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Brain/metabolism/pathology ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; },
abstract = {Microbiota residing in the human gastrointestinal tract play a critical role in maintaining homeostasis through immune regulation, metabolic activity, and signaling to the central nervous system. Recent studies have highlighted the influence of gut microbiota on neurodegenerative diseases, particularly Alzheimer's disease (AD), through the microbiota-gut-brain axis. This bidirectional communication system involves neural, hormonal, and immunological pathways, linking gut health directly with brain function. Disruption of the gut microbial balance-known as dysbiosis-has been associated with increased amyloid-beta (Aβ) deposition, tau hyperphosphorylation, oxidative stress, neuroinflammation, and impaired neurotransmission, all of which are key pathological features of AD. Microbial metabolites such as short-chain fatty acids, trimethylamine N-oxide, and gasotransmitters influence the permeability of the blood-brain barrier and modulate neuroimmune responses. Emerging evidence also indicates that gut microbiota may contribute to the early onset and progression of AD through systemic inflammation and metabolic dysfunction. Modulating the gut microbiome, therefore, presents a novel avenue for therapeutic intervention. This review aims to synthesize current findings on how gut microbiota alterations contribute to AD pathology. Furthermore, it explores therapeutic strategies-including diet, probiotics, prebiotics, polyphenols, and fecal microbiota transplantation-that hold potential in restoring microbial balance and mitigating cognitive decline in AD.},
}

*Alzheimer Disease/therapy/microbiology
Humans
*Gastrointestinal Microbiome/physiology
Animals
*Brain/metabolism/pathology
Dysbiosis
Probiotics/therapeutic use
*Brain-Gut Axis

@article {pmid40516101,
year = {2025},
author = {Saqr, A and Cheng, S and Al-Kofahi, M and Staley, C and Jacobson, PA},
title = {Microbiome-Informed Dosing: Exploring Gut Microbial Communities Impact on Mycophenolate Enterohepatic Circulation and Therapeutic Target Achievement.},
journal = {Clinical pharmacology and therapeutics},
volume = {118},
number = {6},
pages = {1477-1488},
doi = {10.1002/cpt.3740},
pmid = {40516101},
issn = {1532-6535},
mesh = {Humans ; *Mycophenolic Acid/pharmacokinetics/administration & dosage/analogs & derivatives ; *Gastrointestinal Microbiome/drug effects/physiology ; *Enterohepatic Circulation ; *Immunosuppressive Agents/pharmacokinetics/administration & dosage ; Male ; Female ; Middle Aged ; Hematopoietic Stem Cell Transplantation ; Adult ; Models, Biological ; Feces/microbiology ; },
abstract = {Pharmacomicrobiomics is an emerging field due to important microbiome effects on pharmacokinetics and clinical outcomes. However, the application of this knowledge remains limited. Mycophenolic acid (MPA) is the primary active metabolite of the immunosuppressant, mycophenolate mofetil (MMF). MPA undergoes glucuronidation to form MPA glucuronide (MPAG) which is deglucuronidated by bacterial β-glucuronidases and reformed as MPA through enterohepatic circulation (EHC). We studied the stool microbiome effect on the pharmacokinetics of MPA, its metabolites, and EHC in hematopoietic cell transplant (HCT) recipients using a semi-mechanistic population pharmacokinetic model. Microbiome communities were identified using correlation network analysis, and their impact on pharmacokinetics was assessed using full fixed-effects modeling. Simulations were then conducted to evaluate MMF dosing regimens and to assess the impact of community abundance on EHC and MPA therapeutic target achievement. High abundance of Bacteroides uniformis-dominant and Bacteroides vulgatus-dominant communities was associated with higher EHC and an increase in MPA exposure. Low abundance of these communities was associated with a 52-80% and 4-83% lower EHC and MPA exposure, respectively. Simulations showed 70% of individuals with low abundance of these communities achieved the therapeutic target at the typical HCT MMF dose of 1,000 mg Q8 hours IV; however, ≥ 95% were within the therapeutic target at 1,250 mg Q8 hours or 1,750 mg Q12 hours. EHC accounted for 34% of the MPA area under the curve. Elimination of EHC reduced troughs by 100%. This work quantifies the microbiome's effect on pharmacokinetics, paving the way for future microbiome-informed dosing to optimize therapeutic target attainment.},
}

Humans
*Mycophenolic Acid/pharmacokinetics/administration & dosage/analogs & derivatives
*Gastrointestinal Microbiome/drug effects/physiology
*Enterohepatic Circulation
*Immunosuppressive Agents/pharmacokinetics/administration & dosage
Male
Female
Middle Aged
Hematopoietic Stem Cell Transplantation
Adult
Models, Biological
Feces/microbiology

@article {pmid41276052,
year = {2025},
author = {Huan, P and Wang, W and Qi, Y and Sun, J and Zhou, R and Liu, L and Pan, S and Xu, Y and Wang, Z and Zhu, Z and Han, C},
title = {Cynomorium songaricum polysaccharide attenuates high-fat diet-induced testicular dysfunction by modulating the gut microbiota.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {149114},
doi = {10.1016/j.ijbiomac.2025.149114},
pmid = {41276052},
issn = {1879-0003},
abstract = {Obesity disrupts gut microbiota homeostasis and impairs spermatogenesis; however, microbiota-targeted therapies remain insufficiently explored. In this study, a water-soluble polysaccharide(CSP1) was purified from the medicinal plant Cynomorium songaricum. Structural characterization identified CSP1 as a homogeneous α-glucan (Mw 5776 Da) with a backbone of →4)-α-D-Glcp-(1 → residues and C-6 branching. In high-fat diet (HFD)-induced obese mice, CSP1 administration alleviated testicular dysfunction by enhancing sperm count and motility, restoring serum testosterone levels, and ameliorating histopathological damage and germ cell apoptosis. Mechanistically, CSP1 remodeled the gut microbiota composition by suppressing LPS-producing taxa while enriching beneficial populations including SCFA-producing Lachnospiraceae and Bacteroidota. This reshaping reinforced intestinal barrier integrity, as evidenced by the upregulation of ZO-1, occludin, and MUC2. Consequently, CSP1 treatment led to a favorable shift in gut microbiota-derived metabolites, significantly reducing systemic LPS translocation while increasing beneficial short-chain fatty acids (SCFAs) such as acetate and propionate. These changes collectively inhibited testicular TLR4/MyD88/NF-κB activation and downstream pro-inflammatory cytokines (TNF-α, IL-1β). Fecal microbiota transplantation confirmed the causal role of the gut microbiota in mediating CSP1's protective effects. Our findings establish CSP1 as a gut-microbiota-targeting polysaccharide that alleviates obesity-associated male infertility by orchestrating a beneficial remodeling of the gut microbial ecosystem and its metabolic output, offering a novel therapeutic strategy for metabolic reproductive disorders.},
}

@article {pmid41275982,
year = {2025},
author = {Huang, Y and Hu, J and Xu, H and Zhu, R and Liu, L and Chen, X and Sun, Y and Zhao, Y and Zhong, Y and Cheng, B and Huang, X and Lu, H and Xu, ZZ},
title = {Propylparaben Induces Immunotoxicity in Zebrafish via Oxidative Stress and Gut Microbiota-Immune Axis Dysregulation.},
journal = {Fish & shellfish immunology},
volume = {},
number = {},
pages = {111024},
doi = {10.1016/j.fsi.2025.111024},
pmid = {41275982},
issn = {1095-9947},
abstract = {Propylparaben (PP), a widely used preservative, has an unclear immunotoxicity profile. In this study, zebrafish embryos were exposed to 2.5, 5, and 10 μM PP to investigate its developmental and immunological effects. PP induced dose-dependent developmental abnormalities and immunotoxicity. Specifically, it significantly reduced the populations of neutrophils, macrophages, and hematopoietic stem cells (HSCs) in zebrafish embryos. Mechanistically, PP suppressed the TLR4/MyD88/NF-κB pathway and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in embryos, whereas adult zebrafish exhibited marked upregulation of this pathway and these cytokines in intestinal and splenic tissues. PP exposure also elevated reactive oxygen species (ROS) and lipid peroxidation. Co-treatment with the antioxidant astaxanthin (AST) attenuated PP-induced immunotoxicity by reducing ROS level and restoring HSCs, neutrophil, and macrophage populations, confirming oxidative stress as a key mechanism. Furthermore, PP induced gut microbiota dysbiosis and intestinal developmental defects. Exposing germ-free (GF) zebrafish embryos to PP resulted in no significant changes in neutrophils and HSCs, indicating that its immunotoxicity is microbiota-dependent. This was confirmed by fecal microbiota transplantation (FMT), where embryos receiving microbiota from PP-treated donors showed concentration-dependent decreases in neutrophils and HSCs. Our study elucidates the ecological and health risks of PP, advocating for reevaluation of preservative safety and microbiota-targeted mitigation strategies.},
}

@article {pmid41274019,
year = {2025},
author = {Chen, R and Qian, J and Wang, Q and Li, Y and Xu, Z and Zhang, M and Wang, M and Nie, H and Yang, W and Tong, X and Yan, F},
title = {Periodontitis exacerbates metabolic dysfunction-associated steatotic liver disease via the gut microbiota-derived tryptophan metabolism-AHR axis in obesity.},
journal = {EBioMedicine},
volume = {122},
number = {},
pages = {106037},
doi = {10.1016/j.ebiom.2025.106037},
pmid = {41274019},
issn = {2352-3964},
abstract = {BACKGROUND: Periodontitis is linked to metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanisms remain unclear.

METHODS: Periodontitis was investigated in male mice with high-fat diet (HFD)-induced MASLD. Gut microbiome and metabolomic profiling were conducted using16S rRNA gene sequencing, along with both untargeted and targeted metabolomic profiling via liquid chromatography-tandem mass spectrometry. Intestinal barrier integrity was evaluated by histopathological analysis. Faecal microbiota transplantation was conducted and the vital role of the aryl hydrocarbon receptor (AHR) was confirmed using Ahr gene knockout (Ahr[-/-]) mice. The protective roles of tryptophan derivative indole-3-propionic acid (IPA) and the tryptophan-metabolising probiotic Limosilactobacillus reuteri were assessed following their administration via oral gavage. The impact of endotoxin-mediated hyperinflammation on hepatic mitochondrial dynamics was examined in vitro.

FINDINGS: Periodontitis promoted MASLD, gut microbiota dysbiosis, and tryptophan metabolism depletion, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin overexpression in HFD-fed mice. Periodontitis-accelerated MASLD was attenuated in HFD-fed Ahr[-/-] mice. In an AHR-dependent manner, IPA or L. reuteri alleviated the detrimental effects of periodontitis on MASLD progression, intestinal barrier impairment, systemic inflammation, and endotoxin translocation to the liver. Conditioned medium from endotoxin-stimulated THP-1 cells promoted mitochondrial fission in HepG2 cells by upregulating Drp1 expression.

INTERPRETATION: Periodontitis exacerbates MASLD by disrupting the gut microbiota-tryptophan metabolism-AHR axis, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin translocation. Endotoxin plays a pivotal role in promoting hepatic mitochondrial fission during the exacerbation of MASLD by periodontitis. AHR agonists offer a novel intervention strategy for patients with comorbid MASLD and periodontitis.

FUNDING: This work was supported by the Jiangsu Province Key Research and Development Program [No. BE2022670]; National Natural Science Foundation of China [No. 82270979]; Jiangsu Provincial Medical Key Discipline Cultivation Unit [No. JSDW202246]; and High-Level Hospital Construction Project of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University [No. 0224C001].},
}

@article {pmid41273871,
year = {2025},
author = {Jie, L and Liu, J and Liu, Y and Zhang, K and Shen, X and Xu, B and Ji, W and Shi, X},
title = {Sclareol alleviates synovial inflammation in knee osteoarthritis by regulating sphingolipid metabolism along the gut-bone axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157563},
doi = {10.1016/j.phymed.2025.157563},
pmid = {41273871},
issn = {1618-095X},
abstract = {OBJECTIVE: Sclareol(SCL) is a diterpene alcohol compound with anti-inflammatory, antibacterial, and antioxidant properties, and it has high oral bioavailability. However, its pharmacological effects in the field of knee osteoarthritis(KOA) remain unclear.

METHODS: The pharmacological effects of SCL intervention on synovial inflammation in KOA rats were observed using methods such as histopathology and molecular biology. Subsequently, further in vivo and in vitro experiments were conducted to explore the effects of SCL. By combining metabolomics and 16S rRNA sequencing, the impact of SCL on the gut microbiota and metabolic levels was investigated. Based on the results of the omics analyses, the mechanism by which SCL alleviates synovial inflammation in KOA was verified.

RESULTS: Histopathology and molecular biology showed that SCL can significantly improve synovial inflammation and pathological progression in KOA. However, SCL did not exhibit anti-inflammatory effects in vitro experiments or in rats treated with antibiotics. Combined analysis of untargeted metabolomics and 16S RNA-seq indicated that SCL may exert its effects by altering the abundance of bacterial groups like Prevotellaceae ga6a1 group and Corynebacterium and regulating the levels of lipid metabolites such as ceramides. Finally, our combined in vivo and in vitro experiments confirmed that fecal microbiota transplantation (FMT) from SCL-treated rats could modulate gut microbiota composition, reduce sphingolipid metabolism, lower necroptosis levels of synovial macrophages, and decrease inflammation in KOA rats.

CONCLUSION: SCL reduces the abundance of Prevotellaceae ga6a1 group and Corynebacterium decreased levels of ceramides, sphingomyelin, and sphingosine, which in turn lower synovial macrophage necroptosis and synovial inflammation.},
}

@article {pmid41271774,
year = {2025},
author = {Qin, W and Mei, Q and Wang, G and Wang, R and Huang, Z and Fu, Y and Xu, B and Huang, C and Ai, L and Zeng, Y},
title = {Faecalibacterium prausnitzii alleviates experimental recurrent acute pancreatitis by producing oleic acid to regulate MAPK/NF-κB signaling and Th17/Treg balance.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-025-00845-0},
pmid = {41271774},
issn = {2055-5008},
support = {No.82200714//National Natural Science Foundation--Youth Foundation/ ; No. 82300731//National Natural Science Foundation--Youth Foundation/ ; No.10-21-308-420//USST Medical-engineering Cross-project/ ; No. 32025029//National Science Foundation for Distinguished Young Scholars of China/ ; No. 82270671//Natural Science Foundation of China/ ; CCTR-2022B02//Shanghai General Hospital Characteristic Research Program/ ; },
abstract = {Acute pancreatitis (AP) is a complex gastrointestinal disorder associated with disruptions in the gut microbiome. However, the gut microbial and metabolomic profiles in recurrent acute pancreatitis (RAP), which is a clinically distinct subtype of AP, remain unclear. This study integrated microbiome-metabolome analysis to identify the key gut microbial species and metabolic pathways associated with RAP. The findings reveal that the abundance of Faecalibacterium prausnitzii (Fp) is significantly diminished in RAP patients, exhibiting a strong negative correlation with disease severity. Consistent with this observation, fecal microbiota transplantation enriched with Fp significantly ameliorated pancreatic injury in RAP mice. We further isolated Fp Ai 3-16 strain from the stool of healthy volunteers. Functional validation using experimental AP models demonstrates that Fp Ai 3-16 and its metabolite oleic acid (OA) can effectively attenuate pancreatitis by modulating MAPK/NF-κB signaling pathways and restoring the intestinal Th17/Treg balance. Importantly, these results extend beyond the context of RAP, as they highlight the broader significance of the gut-pancreas axis in the pathogenesis of AP. Thus, the elucidation of the underlying molecular mechanisms offers novel therapeutic avenues for RAP management and provides a foundation for further investigations into the intricate interplay between the gut microbiome and the pancreas.},
}

@article {pmid41270737,
year = {2025},
author = {Long, X and Wang, H and Lu, Y and Gao, X and Xiao, Y and Zhang, M and Guo, J and Yang, J and Zhang, R and Li, Q and Zhou, G and Yang, R and Chen, F and Wu, Q and Sun, L and Chu, C and Zhu, X and Wu, Z and Ren, Q and You, C and Liu, Z and Li, Q and Liu, D and Cheng, D and Kang, P and Chen, A and Wu, Q and Fang, Q and Wei, L and Zhang, L and Li, J and Panagiotou, G and Jia, W and Zeng, R and Ni, Y and Chen, L and Li, H},
title = {Interindividual variability in gut microbiome mediates the efficacy of resistant starch on MASLD.},
journal = {Cell metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmet.2025.10.017},
pmid = {41270737},
issn = {1932-7420},
abstract = {Our randomized, placebo-controlled trial showed resistant starch (RS), a type of prebiotic, has therapeutic effects in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we observed its heterogeneous efficacy, where 30% of participants exhibited limited benefits, which was replicated in a multi-center trial (ChiCTR2300074588). Multi-omics analysis and fecal microbiota transplantation identified baseline microbiota as a dominant contributor of response. Further population stratification and network analysis combined with in vitro and in vivo experiments revealed Prevotella as the key cause of low response by inhibiting RS-degrading bacteria, thereby impairing RS utilization. Conversely, Bifidobacterium pseudocatenulatum RRP01, a strain isolated from our cohort, restored RS degradation and improved Prevotella-attenuated RS response. Furthermore, we developed a predictive model integrating baseline microbial and clinical features (area under the curve [AUC] = 0.74-0.87), enabling stratification for personalized interventions. Our study indicates that gut microbiota determines the heterogeneity in RS efficacy and offers possibilities for novel microbiota-oriented precision therapeutics for MASLD.},
}

@article {pmid41270390,
year = {2025},
author = {Chen, L and He, W and Gao, L and Lu, Y and Zhu, L},
title = {Shouhui Tongbian Capsules ameliorate heart failure and atrial fibrillation via gut microbiota regulation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157549},
doi = {10.1016/j.phymed.2025.157549},
pmid = {41270390},
issn = {1618-095X},
abstract = {BACKGROUND: Heart failure (HF) with atrial fibrillation (AF) poses a significant therapeutic challenge due to its complex pathophysiology. Shouhui Tongbian Capsules (SHTB) contain multiple active components that have been proven to affect HF or AF through the intestinal flora. However, the specific therapeutic effects of this drug on HF combined with AF, as well as whether these effects are achieved by regulating the intestinal flora, still require systematic research.

PURPOSE: This study aimed to elucidate the cardioprotective effects of SHTB in a doxorubicin (DOX)-induced HF/AF rat model, focusing on gut microbiota modulation and myocardial transcriptome regulation.

METHODS: Rats were randomized into control, model (DOX-induced HF/AF), SHTB treatment (low/medium/high doses), and metoprolol groups. Pharmacodynamically, cardiac function was assessed via echocardiography and electrocardiography. And myocardial fibrosis was quantitatively evaluated using pathomorphology analysis. Mechanistically, microvascular integrity was examined via immunofluorescence, while the neural activity ligand-receptor interaction pathway-related protein expression was analyzed by immunohistochemistry. Additionally, gut microbiota composition was determined via 16S rRNA sequencing, and myocardial transcriptome profiling was performed using RNA sequencing. Furthermore, fecal microbiota transplantation (FMT) experiments were performed to validate the role of gut microbiota in the observed effects.

RESULTS: The SHTB intervention significantly improved the cardiac function and electrophysiological stability of HF/AF rats, along with enhancing microvascular maturation and reducing myocardial fibrosis. The analysis of the intestinal microbiota showed that SHTB effectively restored the microbial ecological balance, especially regulating the abundance of key genera (such as Turicibacter) closely related to disease progression and treatment efficacy. Transcriptional analysis identified the neural activity ligand-receptor pathway as the key mechanism, and FMT experiments demonstrated that SHTB modulates the Edn1-Agtr1a-Bdkrb2 axis through gut microbiota, ultimately leading to improved cardiac function. The synergistic effect of the composition of the intestinal microbiota and myocardial molecular targets jointly contributed to the improvement of cardiac remodeling in HF/AF.

CONCLUSION: SHTB ameliorates HF with AF by synergistically modulating the gut-heart axis, involving gut microbiota restoration, myocardial fibrosis suppression, and vascular tension regulation via the Edn1-Agtr1a-Bdkrb2 axis. This multi-target mechanism substantiates SHTB's potential as a promising adjunct therapy for HF/AF.},
}

@article {pmid41270389,
year = {2025},
author = {Zheng, M and Meng, Y and Feng, J and Liang, H and Mu, X and Feng, C},
title = {Shenling Baizhu Powder potentiates immunotherapy response: putative roles of gut microbial remodeling and fatty acid metabolism modulation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157559},
doi = {10.1016/j.phymed.2025.157559},
pmid = {41270389},
issn = {1618-095X},
abstract = {BACKGROUND: Low response rates and immune-related adverse events (irAEs) are major factors affecting the efficacy of PD-1 monoclonal antibody (mAb) immunotherapy in NSCLC. Modulating the gut microbiota-immune-tumor axis is considered a key strategy to overcome these challenges.

PURPOSE: This study aimed to investigate whether Shenling Baizhu powder (SLBZS), a traditional Chinese medicine formula, could enhance the efficacy of PD-1 mAb immunotherapy and mitigate irAEs by regulating gut microbiota and host metabolism.

STUDY DESIGN: Two experimental models were employed: (1) a standard Lewis subcutaneous tumor mouse model to evaluate therapeutic effects and irAEs, and (2) a lung metastasis model using bioluminescence imaging to assess tumor progression. Additionally, an antibiotic-cleared mouse model combined with fecal microbiota transplantation (FMT) was used to validate gut microbiota-mediated mechanisms.

METHODS: Subcutaneous tumor growth, organ toxicity, and metastasis were monitored in vivo. Multi-omics approaches included fecal 16S rDNA sequencing, untargeted/targeted plasma metabolomics, and immune profiling of splenic and tumor microenvironment (TME) lymphocytes. SLBZS/FMT interventions were applied to antibiotic-treated mice to assess microbiota-dependent effects.

RESULTS: SLBZS synergized with PD-1 mAb to significantly inhibit tumor growth and reduce multi-organ irAEs. In the metastasis model, SLBZS suppressed early tumor implantation and late-stage dissemination. Multi-omics analyses revealed that SLBZS enriched beneficial gut bacteria (e.g., Akkermansia, Lactobacillus, Muribaculum) and microbial metabolites, including short-chain fatty acids (SCFAs), while enhancing anti-tumor T-cell subsets in the spleen and TME. Critically, SLBZS/FMT restored gut microbiota homeostasis and reversed antibiotic-induced immunotherapy resistance.

CONCLUSION: SLBZS, as a traditional Chinese medicinal formulation, enhances the efficacy of PD-1 mAb through a unique dual-regulatory mechanism. It concurrently remodels the gut microbiota structure and optimizes the metabolic microenvironment, with these synergistic actions collectively amplifying anti-tumor immunity while reducing irAEs. This dual-mode efficacy distinguishes SLBZS from conventional microbial modulators that solely target microbiota without metabolic coordination. Our study provides the first experimental validation of SLBZS as a clinically valuable adjuvant of Chinese medicinal origin for NSCLC immunotherapy. Furthermore, we pioneer a novel research paradigm integrating traditional Chinese medical theory with the "microbiota-metabolism-immune network" axis, thereby offering innovative therapeutic strategies for refining cancer immunotherapies.},
}

@article {pmid41270175,
year = {2025},
author = {Liu, W and Yang, J and Wei, Z and Kong, W and Dong, Z and Wei, Y and Zhuang, J and Qi, J},
title = {miRNA-loaded biomimetic nanoparticles orchestrate gut microbe to ameliorate inflammatory bowel disease.},
journal = {Science advances},
volume = {11},
number = {47},
pages = {eadw5984},
doi = {10.1126/sciadv.adw5984},
pmid = {41270175},
issn = {2375-2548},
mesh = {*MicroRNAs/genetics/chemistry/administration & dosage ; *Nanoparticles/chemistry ; Animals ; *Inflammatory Bowel Diseases/microbiology/therapy/pathology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Mice ; Lacticaseibacillus rhamnosus/metabolism/genetics ; Extracellular Vesicles/metabolism ; *Biomimetic Materials/chemistry ; Disease Models, Animal ; Humans ; Colitis/pathology ; Biomimetics ; Probiotics ; },
abstract = {Modulation of gut microbiota has emerged as a promising therapeutic strategy for inflammatory bowel disease (IBD). However, current interventions such as probiotics and fecal microbiota transplantation remain limited by insufficient safety and efficacy. To address this, we engineered commensal Lactobacillus rhamnosus (LGG) using miRNA-loaded biomimetic nanoparticles to enhance its proliferation and indole-3-carboxaldehyde production. By functionalizing bacterial extracellular vesicles (BEVs) derived from LGG with lipid nanoparticles (LNPs), we developed BEV-LNPs that exhibited enhanced targeting efficiency toward LGG compared to Escherichia coli. In vitro and in vivo studies demonstrated that BEV-LNPs showed superior stability in simulated physiological fluids and gastrointestinal environments compared to conventional LNPs. When combined with 5-aminosalicylic acid, the BEV-LNP formulation notably improved outcomes in acute and chronic colitis models, reducing inflammation, restoring epithelial barrier integrity, and promoting microbial balance. This study presents an effective strategy for colitis treatment by leveraging miRNA-loaded nanoparticles.},
}

*MicroRNAs/genetics/chemistry/administration & dosage
*Nanoparticles/chemistry
Animals
*Inflammatory Bowel Diseases/microbiology/therapy/pathology/drug therapy
*Gastrointestinal Microbiome/drug effects
Mice
Lacticaseibacillus rhamnosus/metabolism/genetics
Extracellular Vesicles/metabolism
*Biomimetic Materials/chemistry
Disease Models, Animal
Humans
Colitis/pathology
Biomimetics
Probiotics

@article {pmid41269489,
year = {2025},
author = {Lapauw, L and Amini, N and Switsers, E and Dupont, J and Vercauteren, L and Derrien, M and Raes, J and Gielen, E},
title = {Effect of host and gut microbiota-altering interventions on sarcopenia or its defining parameters: a systematic review and meta-analysis of nutrition-based intervention studies.},
journal = {Aging clinical and experimental research},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40520-025-03216-z},
pmid = {41269489},
issn = {1720-8319},
abstract = {AIM: To investigate effects of host- and gut microbiota (GM)-altering interventions on sarcopenia (parameters).

METHODS: Upon PROSPERO registration (CRD42022347363), six databases and one registry were searched until January 5th 2024 and updated on June 10th 2025 for diet, pre-, pro-, or synbiotics mono-interventions in populations with mean age ≥ 50 years. (Standardized) mean differences (SMD) and 95% confidence intervals (CI) were computed using random-effects models if heterogeneity was > 50%. Risk of bias (Rob) & GRADE assessments were carried out to assess the evidence' quality and certainty.

RESULTS: The qualitative analysis included 38 diet, 13 prebiotics, 11 probiotics and 1 synbiotics studies, totaling 4842 participants (59%♀), mostly of high RoB. The quantitative analysis included 49 studies. Probiotics improved muscle strength by 1.90 kg and gait speed by 0.08 m/s. Fiber (whole-food)-enriched diets improved muscle strength with 1.25 kg and energy-restricted diets, aimed at weight loss, improved muscle mass if mean age was < 60 years and if the intervention lasted no longer than 12 weeks. High-protein diets improved muscle mass in women and if the intervention lasted at least 12 weeks. Studies involving participants with sarcopenia were only included in the qualitative analysis, since none provided sufficient data to allow a quantitative synthesis.

DISCUSSION: Fiber (whole food)-enriched diets and probiotics improve muscle strength. The latter intervention also improves gait speed. High-protein diets improve muscle mass in women and with intervention durations ≥ 12 weeks. Future studies should include fecal sampling to assess whether GM modulate the observed effects.

CONCLUSION: Specific diets and probiotics offer potential to improve sarcopenia parameters.},
}

@article {pmid41269457,
year = {2025},
author = {Younis, NK and Alfarttoosi, KH and Sanghvi, G and Roopashree, R and Kashyap, A and Krithiga, T and Taher, WM and Alwan, M and Jawad, MJ and Ali Al-Nuaimi, AM},
title = {Attenuating Neurotoxicity Through Fecal Microbiota Transplant: Mechanisms and Therapeutic Potential.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {128},
pmid = {41269457},
issn = {1559-1182},
mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; *Neurotoxicity Syndromes/therapy/microbiology ; },
abstract = {Neurotoxicity, triggered by drugs, environmental pollutants, metabolic disorders, or infections, can cause lasting neurological dysfunction and cognitive impairment. Recent research highlights the gut microbiota's crucial role in regulating brain health and vulnerability to neurotoxic damage, sparking interest in fecal microbiota transplantation (FMT) as a potential treatment. This review examines how FMT may counteract neurotoxicity and assesses its therapeutic potential for neurodegenerative diseases, neuroinflammation, and cognitive decline. The gut-brain axis-a bidirectional communication system between the gut and the central nervous system (CNS)-acts as the primary route through which gut microbes influence brain function. Growing evidence suggests that microbiota imbalances can exacerbate neuroinflammation, oxidative stress, blood-brain barrier disruption, and altered neurotransmitter production, all of which contribute to neurotoxicity. FMT, the transfer of donor fecal microbes to a recipient's gut, has demonstrated promise in restoring microbial equilibrium and reducing neurotoxic effects in both animal studies and human trials. The review also explores microbial profiles tied to neuroprotection versus those linked to neurotoxic conditions, along with the prospects of tailored microbiome therapies. Despite its potential, FMT faces challenges, including protocol standardization, donor selection criteria, and long-term efficacy. More research is needed to unravel the intricacies of gut-brain interactions and optimize FMT for clinical use. If these hurdles are addressed, FMT could become a transformative therapy for neurotoxicity-related disorders.},
}

*Fecal Microbiota Transplantation/methods
Humans
Animals
*Gastrointestinal Microbiome/physiology
*Neurotoxicity Syndromes/therapy/microbiology

@article {pmid41268538,
year = {2025},
author = {Jiao, JM and Liu, CG and Zang, D and Chen, J},
title = {Gut microbiota and metabolites: emerging prospects in the treatment of non-small cell lung cancer.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1638942},
pmid = {41268538},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Carcinoma, Non-Small-Cell Lung/therapy/metabolism/microbiology ; *Lung Neoplasms/therapy/metabolism/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; },
abstract = {Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, accounting for approximately 85% of all cases, and is associated with a poor prognosis. Despite significant advancements in treatment modalities, therapeutic efficacy remains suboptimal, underscoring the urgent need for novel strategies. In recent years, increasing attention has been directed toward the pivotal role of gut microbiota-host interactions in the treatment of NSCLC. This review systematically examines the influence of current NSCLC therapies on gut microbiota and metabolism, explores the relationship between the microbiome and therapeutic response, and highlights the critical functions of probiotics, microbial metabolites, fecal microbiota transplantation (FMT), and dietary interventions in NSCLC management. By elucidating the mechanisms through which gut microbiota and their metabolites modulate treatment efficacy, we investigate the potential of exogenous interventions targeting the gut ecosystem to enhance therapeutic outcomes and mitigate adverse effects. Modulating the intestinal microbiota represents a promising clinical avenue and offers a new frontier for the development of future NSCLC treatment strategies.},
}

Humans
*Gastrointestinal Microbiome/drug effects
*Carcinoma, Non-Small-Cell Lung/therapy/metabolism/microbiology
*Lung Neoplasms/therapy/metabolism/microbiology
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Animals

@article {pmid41268164,
year = {2025},
author = {Zhao, M and Chen, D and Hu, X and Xie, C and Xu, L and Zhou, F},
title = {Gut-ovary axis in polycystic ovary syndrome: mechanistic insights and gut microbiota-targeted therapeutic strategies.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1684492},
pmid = {41268164},
issn = {1664-2392},
mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/therapy/metabolism ; *Gastrointestinal Microbiome/physiology ; Female ; Probiotics/therapeutic use ; *Ovary/metabolism ; Fecal Microbiota Transplantation/methods ; },
abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that significantly affects women's reproductive health and quality of life. Its pathogenesis involves multiple factors, including genetics, environment, and metabolism. In recent years, with the growing body of research on PCOS, the "gut-ovary axis" hypothesis has become a prominent research focus. This hypothesis suggests that an imbalance in gut bacteria may significantly influence the onset and progression of PCOS through various pathways, such as immune regulation, metabolic disturbances, and hormonal imbalances. This article aims to review the role of the "gut-ovary axis" in PCOS and to explore novel treatment strategies based on gut microbiota modulation, including probiotics, fecal microbiota transplantation, and dietary interventions. These strategies represent promising research avenues for future PCOS treatments, with preliminary studies demonstrating their potential to improve clinical symptoms. However, it is crucial to note that these are not yet established therapies and require substantial further validation. Novelty and Significance of this Review: This review moves beyond a descriptive catalog of associations to provide a critical appraisal of the gut-ovary axis in PCOS. We systematically differentiate well-established mechanisms from speculative hypotheses, explicitly identify persistent knowledge gaps, and evaluate the translational potential of microbiota-targeted therapies, thereby offering a refined framework for future basic and clinical research.},
}

Humans
*Polycystic Ovary Syndrome/microbiology/therapy/metabolism
*Gastrointestinal Microbiome/physiology
Female
Probiotics/therapeutic use
*Ovary/metabolism
Fecal Microbiota Transplantation/methods

@article {pmid41267780,
year = {2025},
author = {Sharma, I and Sudarsanan, D and Moonah, S},
title = {The gut microbiome as a major source of drug-resistant infections: emerging strategies to decolonize and target the gut reservoir.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1692582},
pmid = {41267780},
issn = {2235-2988},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Bacterial Infections/microbiology/therapy/prevention & control ; *Drug Resistance, Bacterial ; Phage Therapy ; *Bacteria/drug effects ; Antimicrobial Peptides/therapeutic use ; },
abstract = {Infections caused by antimicrobial-resistant bacteria represent a significant global health crisis that continues to worsen, creating an urgent need for alternative treatment and prevention strategies. A major source of drug-resistant bacteria is the human gut. The gut microbiota consists of bacteria that are frequently exposed to antibiotics, leading to selective pressure that promotes the development of resistant strains such as carbapenem-resistant Enterobacterales (CRE) and vancomycin-resistant enterococci (VRE). These drug-resistant bacteria can spread from the gut to other body sites, leading to hard-to-treat and potentially life-threatening infections such as bacteremia, surgical site infections, and urinary tract infections. Targeting the gut reservoir is essential in the fight against antimicrobial resistance. In this review, we focus on emerging non-antibiotic strategies aimed at eliminating drug resistant bacteria from the gut before they cause invasive infections, with particular emphasis on clinical evidence. Approaches discussed include fecal microbiota transplantation, bacteriophage therapy, antimicrobial peptides, probiotics, and dietary interventions. Optimizing these strategies, while continuing to explore newer approaches, will be essential to combat the growing threat of drug-resistant infections.},
}

Humans
*Gastrointestinal Microbiome/drug effects
Anti-Bacterial Agents/pharmacology/therapeutic use
Fecal Microbiota Transplantation
Probiotics/therapeutic use
*Bacterial Infections/microbiology/therapy/prevention & control
*Drug Resistance, Bacterial
Phage Therapy
*Bacteria/drug effects
Antimicrobial Peptides/therapeutic use

@article {pmid41265661,
year = {2025},
author = {Cao, P and Li, Y and Zhang, S and Li, C and Sun, Y and An, B},
title = {Study on the efficacy and mechanism of fecal microbiota transplantation for depression based on circadian rhythm.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106186},
doi = {10.1016/j.bbi.2025.106186},
pmid = {41265661},
issn = {1090-2139},
abstract = {BACKGROUND: Depression is closely associated with disruptions in circadian rhythms, and emerging evidence highlights critical roles of gut dysbiosis in its pathogenesis. However, the mechanisms by which FMT chronotherapy influences circadian gene in depression-via gut microbiota-remain poorly understood.

METHODS: In this study, we established a chronic unpredictable mild stress (CUMS) mouse model and performed fecal microbiota transplantation (FMT) using donor microbiota from healthy mice at two distinct circadian time points-zeitgeber time (ZT) 4 or ZT16 to identify the optimal timing for FMT based on behavioral assessments. Integrating omics dependent mechanisms of antidepressant effects mediated by these key functional bacteria.

RESULTS: Health-FMT significantly alleviated depressive-like behaviors, with superior efficacy at ZT4. It restored circadian gene expressions and attenuated neuroinflammation expression in the hippocampus and prefrontal cortex. 16S rRNA sequencing revealed that Health-FMT reduced uncultured_bacterium_g_Alistipes abundance, a genus linked to tryptophan availability. Tryptophan supplementation regulated circadian gene expressions, inflammatory factors, brain-derived neurotrophic factors (BDNF), microglial and astrocytic activation, and exerted antidepressant effects via the ERK signaling pathway.

CONCLUSIONS: These findings suggest that Health-FMT exerts antidepressant effects by restoring gut homeostasis, particularly by reducing Alistipes, thereby rebalancing tryptophan metabolic and circadian gene expressions. These findings offer a new possible mechanism and novel insights into the microbiota-gut-brain axis in depression, and underscore the importance of chronotherapy in FMT-based therapeutic strategies.},
}

@article {pmid41265501,
year = {2025},
author = {Yan, S and Xie, Y and Xv, J and Wang, K and Wang, J and Cao, Y and Han, X and Chen, F and Zhou, L and Jiang, Y and Liu, Y},
title = {Shengjiang San attenuates sepsis-induced acute intestinal injury via Lactobacillus murinus derived IAAld-mediated macrophage polarization through NF-κB and TGF-β signaling.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {120910},
doi = {10.1016/j.jep.2025.120910},
pmid = {41265501},
issn = {1872-7573},
abstract = {ETHNOPHARMACOLOGY ASSOCIATED: Sepsis is a life-threatening condition triggered by a dysregulated host response to infection, characterized by uncontrolled systemic inflammation and often culminating in multiple organ damage. Shengjiang San (SJS), a classic traditional Chinese medicinal (TCM) formula, has been historically utilized for its efficacy in removing heat, resolving toxicity, and reducing inflammation. Nevertheless, the precise role and mechanisms through which SJS modulates inflammatory responses and protects against sepsis-induced multi-organ injury are not yet fully understood.

OBJECTIVE: To investigate the protective mechanisms of SJS that improve sepsis-induced acute intestinal injury (SAII) by modulating the abundance and metabolism of the gut microbiota.

METHODS: A sepsis animal model was established using cecal ligation and puncture. The protective effects of SJS in SAII were evaluated through behavioral assessments, enzyme-linked immunosorbent assay, histological examination, and immunofluorescence analysis. Fecal samples were subjected to 16S rRNA sequencing and non-targeted metabolomics to identify probiotic taxa and metabolites associated with SJS administration. Proteomic analysis integrated with network pharmacology was performed to explore the underlying mechanisms. Fecal microbiota transplantation (FMT) and microbial metabolite analysis were utilized to elucidate the potential mechanism.

RESULTS: SJS was observed to significantly improve clinical scores, reduce pro-inflammatory cytokines, including IL-6, TNF-α and IL-1β. SJS also restored integrity of the intestinal barrier by upregulating the expression of ZO-1 and Claudin-1. 16S rRNA sequencing analysis demonstrated that SJS induced significant restructuring of the gut microbiota, including a marked increase in Lactobacillus murinus (L.M.) abundance. Proteomic and network pharmacological analyses revealed that SJS was protected against SAII by inhibiting NF-κB-mediated M1 polarisation while promoting TGF-β-mediated M2 polarisation. In particular, this protective effect was found to depend on the abundance of L.M., which regulated intestinal inflammation through its specific metabolites, indoleacetaldehyde (IAAld).

CONCLUSION: SJS improves SAII by orchestrating L.M. derived IAAld-mediated macrophage polarization through modulation of NF-κB and TGF-β signaling pathways.},
}

@article {pmid41263913,
year = {2025},
author = {Merrick, B and Prossomariti, D and Kertanegara, M and Wyatt, D and Goldenberg, S},
title = {Facilitators and barriers to recruitment and retention in a feasibility trial of encapsulated faecal microbiota transplant to eradicate carriage of antibiotic-resistant bacteria at an academic hospital in central London: a nested qualitative study.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e104783},
doi = {10.1136/bmjopen-2025-104783},
pmid = {41263913},
issn = {2044-6055},
mesh = {Humans ; London ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Feasibility Studies ; Middle Aged ; Qualitative Research ; Adult ; Focus Groups ; *Patient Selection ; COVID-19/epidemiology ; Aged ; *Carrier State/therapy ; },
abstract = {OBJECTIVES: This nested qualitative study (NQS) aimed to identify facilitators and barriers to the delivery of a substantive randomised controlled trial investigating the eradication of gastrointestinal tract carriage of antibiotic-resistant organisms using encapsulated faecal microbiota transplant (FMT).

DESIGN: NQS within a participant-blinded, randomised, placebo-controlled, single-centre, feasibility trial (RCT)-Feasibility of ERadicating gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO) (ISRCTN reg. no. 34 467 677)-with data collected via focus groups and analysed using thematic analysis.

SETTING: RCT participants were recruited from a large academic tertiary referral hospital in central London. Focus groups were held at the hospital or via videoconferencing for those unable to travel.

PARTICIPANTS: This study included 13 FERARO study participants across two focus groups. 11 participants were under RCT follow-up and unaware of their treatment allocation, two participants had completed 6-month follow-up and knew whether they had received FMT or matched placebo. Additional data were opportunistically collected on reasons for declining RCT participation.

RESULTS: Participants found FMT to be an acceptable and holistic management strategy and noted positive impacts from RCT participation including enhanced personal health awareness and valuable support from the research team. The time and travel commitment presented the most substantial barrier to RCT participation. Many participants were motivated by a desire to give something back to the UK National Health Service and/or research. Patients' current health status also influenced the decision-making process, and, while infrequently cited, the COVID-19 pandemic added extra complexity likely impacting individuals' willingness to participate.

CONCLUSIONS: While FMT is generally acceptable to participants, logistical barriers such as the time and travel commitment associated with RCT participation need consideration. Effective communication, personal connections and participant education on antimicrobial resistance are likely to be crucial for enhancing recruitment and retention in future trials.

TRIAL REGISTRATION NUMBER: ISRCTN registration number 34 467 677 and EudraCT number 2019-001618-41.},
}

Humans
London
*Fecal Microbiota Transplantation/methods
Male
Female
Feasibility Studies
Middle Aged
Qualitative Research
Adult
Focus Groups
*Patient Selection
COVID-19/epidemiology
Aged
*Carrier State/therapy

@article {pmid41263574,
year = {2025},
author = {Tang, L and Xie, P and Wang, H and Hong, X and Gong, Z and Zhao, G and Yue, M},
title = {The sex hormone-gut microbiome axis: mechanistic drivers of sex-disparate bacterial infection outcomes and precision clinical interventions.},
journal = {Clinical microbiology reviews},
volume = {},
number = {},
pages = {e0023625},
doi = {10.1128/cmr.00236-25},
pmid = {41263574},
issn = {1098-6618},
abstract = {SUMMARYSex disparities in bacterial infections pose significant challenges in clinical microbiology, influencing diagnostic approaches, antimicrobial stewardship, and patient outcomes. Males frequently exhibit heightened severity in conditions like Helicobacter pylori-associated gastritis and Vibrio cholerae outbreaks, whereas females face amplified risks during reproductive phases for pathogens, such as Listeria monocytogenes and Salmonella spp. Beyond genetic and behavioral factors, the bidirectional sex hormone-gut microbiome axis emerges as a key mechanistic driver: estrogens bolster innate immunity and microbial diversity (e.g., enriching short-chain fatty acid-producing taxa like Bifidobacterium), while androgens and progesterone impose immunosuppressive effects, altering colonization resistance and virulence modulation. Microbial contributions-via β-glucuronidase-mediated hormone deconjugation, bile acid biotransformations, and metabolite signaling-further calibrate host responses, as evidenced in Clostridioides difficile recurrence and enterohemorrhagic Escherichia coli virulence upregulation. This review synthesizes epidemiological, preclinical, and emerging clinical data, highlighting the axis's role in pathogen-specific immune evasion and dysbiosis-driven exacerbations. Clinically, these insights advocate for sex-stratified microbiome diagnostics (e.g., 16S rRNA sequencing for risk profiling) and targeted therapies, including hormone-modulated probiotics to restore barrier function, fecal microbiota transplantation to curb antibiotic-associated vulnerabilities, and selective estrogen receptor modulators to enhance clearance in high-risk cohorts. Despite advances, gaps in human longitudinal studies and pathogen-strain interactions limit translation. Future research integrating multi-omics with clinical trials could refine precision interventions, optimizing infection management in diverse populations and aligning with evolving demands for personalized microbiology.},
}

@article {pmid41263392,
year = {2025},
author = {Zhao, R and Lu, Y and Xu, Q and Ren, H and Li, H and Gao, J and Cui, H and Yuan, Z and Cao, B and Wei, B},
title = {Gut blautia coccoides-derived 5Z-dodecenoic acid attenuates chronic psychological stress-induced gastric cancer progression.},
journal = {International journal of surgery (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/JS9.0000000000004080},
pmid = {41263392},
issn = {1743-9159},
abstract = {BACKGROUND: Chronic psychological stress is a critical oncogenic factor of gastric cancer (GC). However, the mechanisms underlying stress-induced malignant progression remain largely unknown. Gut microbiota dysregulation is tightly associated with cancer development and metabolism.

MATERIALS AND METHODS: Chronic unpredictable mild stress (CUMS) modeling was used to prepare mice suffering from chronic psychological stress. 16s rRNA sequencing and Q300 targeted metabolite quantification were jointly conducted to depict landscapes of gut microbiome and metabolomics of CUMS mice. Fecal microbiota transplantation was employed to investigate the functions of gut microbial communities in regulating CUMS-mediated GC growth. Drug affinity responsive target stability, surface plasmon resonance and molecular docking assays were performed to screen direct target proteins of 5Z-dodecenoic acid. The interactions between RIOK2 and BYSL were verified with co-immunoprecipitation and GST pull-down and fluorescent co-localization analysis. A series of experiments for malignant behaviors and glycolysis and subcutaneous tumor transplantation were employed to detect alterations of GC cell phenotypes ex vivo and in vivo, respectively.

RESULTS: Microbiome and metabolomics collectively demonstrated disrupted gut microbial communities and metabolic patterns. Particularly, Blautia coccoides-derived 5Z-dodecenoic acid was predominately declined by CUMS. Supplementation with Blautia coccoides or 5Z-dodecenoic acid effectively mitigated the negative effects of CUMS on glycolysis and malignancy. Mechanistically, 5Z-dodecenoic acid directly inhibits the functions of RIOK2, which maintained ectopic glycolysis and malignant behaviors. RIOK2 further interacted with BYSL and maintained its properties of potentiation of GC progression and metabolism.

CONCLUSION: Our findings advance the insights of Blautia coccoides-derived 5Z-dodecenoic acid implicated in chronic psychological stress-induced GC progression and provide novel strategies for dampening GC progression.},
}

@article {pmid41263038,
year = {2025},
author = {Wang, M and Sun, H and Wang, X and Zhang, X and Huang, Y and Cui, R and Sun, Y and Yao, H and Wan, JY},
title = {Tangerine Peel-Based Herbal Formula Ameliorates Metabolic Syndrome via Gut Microbiota-Mediated Bile Acid Remodeling and TGR5 Activation.},
journal = {The American journal of Chinese medicine},
volume = {},
number = {},
pages = {1-19},
doi = {10.1142/S0192415X25500946},
pmid = {41263038},
issn = {1793-6853},
abstract = {The growing global burden of metabolic syndrome (MetS), a key driver of multiple chronic diseases, highlights the limited treatment options for its multifactorial pathophysiology. Tanshi-Tiaoti Decoction (TTD), a Chinese herbal formula comprised of Citri Reticulatae Pericarpium (Tangerine peel), Coicis Semen (Raw coix seed/Job's tears), Raphani Semen (Radish seed), Nelumbinis Folium (Lotus leaf), Eckloniae/Laminariae thallus (Kelp), and Crataegi Fructus (Raw hawthorn fruit), demonstrates efficacy in the clinical management of MetS. However, its underlying molecular mechanisms remain incompletely elucidated. This study indicates that TTD restored gut microbiota homeostasis and bile acid (BA) profiles in high-fat diet (HFD)-induced MetS mice. TTD significantly attenuated body weight gain, fasting glucose levels, serum triglycerides, and hepatic steatosis. TTD corrected gut microbiota dysbiosis, most notably by reducing the Firmicutes/Bacteroidetes ratio. Fecal microbiota transplantation (FMT) validated the fact that the gut microbiome mediates TTD's therapeutic effects. TTD regulated BA biosynthesis through this microbial modulation, and thus specifically increased hyodeoxycholic acid (HDCA). HDCA, which has been identified as the signature BA during TTD treatment, phenocopied TTD's therapeutic effects against MetS by both activating the BA receptor TGR5 and subsequently promoting beige adipocyte browning. Collectively, TTD ameliorates MetS by reshaping microbial-mediated BA pools, and in particular elevates HDCA levels to thereby activate TGR5 and induce beige adipocyte browning. These findings support TTD as a promising herbal-based therapeutic strategy for the treatment of MetS.},
}

@article {pmid41260222,
year = {2025},
author = {Wang, Y and Wu, J and Yao, J and Chen, J and Cheng, KKY and Ho, MY and Lee, CH and Lam, KS and Tse, MA and Panagiotou, G and Xu, A},
title = {Gut microbiome-adipose crosstalk modulates soluble IL-6 receptor influencing exercise responsiveness in glycemic control and insulin sensitivity.},
journal = {Cell metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmet.2025.10.013},
pmid = {41260222},
issn = {1932-7420},
abstract = {Exercise is an effective intervention for the prevention and management of diabetes, but the high interpersonal variability in response to exercise impedes its widespread implementation. Herein, we identify adipocyte-derived soluble interleukin-6 receptor (sIL-6R) as a key exerkine determining exercise efficacy in improving metabolic health. In individuals with obesity who underwent a 12-week exercise intervention, circulating sIL-6R level exhibits dichotomous changes between exercise responders (Rs) and non-responders (NRs), in close association with exercise-mediated alterations in insulin sensitivity and glycemic control. Mechanistically, elevated gut microbiome-mediated leucine in NR acts on white adipocytes to promote disintegrin and metalloproteinase 17 (ADAM17)-mediated sIL-6R production via the mammalian target of rapamycin (mTOR)-hypoxia-inducible factor 1α (HIF1α) pathway, which in turn impairs the metabolic benefits of exercise through interleukin (IL)-6 trans-signaling-induced adipose inflammation. Adipocyte-selective ablation of ADAM17 prevents the effects of fecal microbiota transplantation from NR on elevation of sIL-6R, thereby restoring the efficacy of exercise-shaped gut microbiome in counteracting glucose intolerance and insulin resistance in obese mice. Thus, therapeutic interventions targeting adipocyte-derived sIL-6R represent a promising strategy for maximizing exercise efficacy in personalized diabetes prevention.},
}

@article {pmid41258493,
year = {2025},
author = {Xu, Q and Lin, A and Jiang, A and Chen, L and Zhu, L and Mou, W and Liu, Z and Zhang, J and Cheng, Q and Miao, K and Luo, P},
title = {Circadian rhythms as a modulator of gut microbiota-tumor microenvironment crosstalk.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {82},
number = {1},
pages = {409},
pmid = {41258493},
issn = {1420-9071},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Circadian Rhythm/physiology ; *Tumor Microenvironment ; Animals ; *Neoplasms/microbiology/pathology/therapy ; Dysbiosis/microbiology ; },
abstract = {Circadian rhythms play a pivotal role in regulating diverse physiological functions, notably the composition and activity of gut microbiota. Accumulating evidence indicates that circadian rhythm disruption can induce dysbiosis of the gut microbiome, which in turn is implicated in influencing the tumor microenvironment (TME) and facilitating cancer progression. This review integrates and analyzes recent advances elucidating the complex interplay where circadian rhythms modulate gut microbiota, and how these circadian-driven microbial changes affect the TME. This review analyzes recent advances in elucidating the complex interplay among circadian rhythms, gut microbiota, and the TME. We examine how circadian disruption modifies the diversity and metabolic functions of gut microbiota, resulting in alterations of microbial metabolites, including but not limited to short-chain fatty acids and secondary bile acids. These metabolic alterations have the potential to modulate immune cell function, vascular remodeling, and tumor cell metabolism within the TME. We investigate the potential mechanisms through which gut microbial dysbiosis induced by circadian misalignment could promote an immunosuppressive TME and accelerate tumor growth. Additionally, we evaluate emerging therapeutic strategies that leverage the circadian-microbiome axis, encompassing chronotherapy, probiotic supplementation, and fecal microbiota transplantation. The integration of circadian biology, microbiology, and cancer immunology presents promising avenues for the development of novel diagnostic and therapeutic approaches. However, significant challenges persist in translating these findings into viable clinical applications. Further research is imperative to elucidate the molecular pathways interconnecting circadian rhythms, gut microbiota, and the TME, and to develop personalized chronobiological interventions for cancer prevention and treatment.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Circadian Rhythm/physiology
*Tumor Microenvironment
Animals
*Neoplasms/microbiology/pathology/therapy
Dysbiosis/microbiology

@article {pmid41255657,
year = {2025},
author = {Vaou, N and Zavras, N and Fessatou, S and Voidarou, CC and Vrioni, G and Tsakris, A and Vaos, G},
title = {Microbiota decolonization of bacterial pathogens in pediatric surgery-related intestinal disorders: Insights on current strategies and future outlook.},
journal = {World journal of clinical pediatrics},
volume = {14},
number = {4},
pages = {107722},
pmid = {41255657},
issn = {2219-2808},
abstract = {The significance of gut microbiota (GM) in human health is being increasingly researched. An imbalance in GM composition, known as dysbiosis, is linked to various and other health issues. In addition, antibiotics are the primary and most significant factors leading to major changes in the composition and function of the GM, which may result in colonization by antimicrobial-resistant (AMR) pathogens. Therefore, alternative antibiotic strategies for combating AMR pathogens are urgently needed. This narrative review highlights current knowledge regarding various pertinent strategies for decolonizing bacterial pathogens from GM and emphasizes decolonization therapies' critical role in pediatric surgical disorders. Strategies such as decontamination of the digestive tract utilizing antibiotics, the use of probiotics, and particularly fecal microbiota transplantation have introduced new options for clinical treatment. These treatments show the potential to restore GM balance and have demonstrated advantages for intestinal disorders related to pediatric surgery, including inflammatory bowel disease, neonatal necrotizing enterocolitis, Hirschsprung-associated enterocolitis, and short bowel syndrome. Despite GM therapeutics, recent strategies are still in their developmental phase and exhibit challenges that need further research. Thus, potential future directions for GM-targeted decolonization therapies are under consideration. Innovative alternative strategies to combat AMR though GM modulation in disorders related to pediatric surgery appear to be promising and should continue to be prioritized for further research and development.},
}

@article {pmid41255529,
year = {2025},
author = {Horiachok, M and Potapova, K and Ivanykovych, T and Yerokhovych, V and Ilkiv, Y and Sokolova, L},
title = {Integrating gut microbiota into multidisciplinary perspectives on diabetic neuropathy.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1710868},
pmid = {41255529},
issn = {1664-2392},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetic Neuropathies/microbiology/therapy/metabolism ; *Dysbiosis/microbiology ; Animals ; Probiotics/therapeutic use ; },
abstract = {Diabetic neuropathy (DN) is one of the most common and debilitating complications of diabetes mellitus, yet its precise pathogenesis remains incomplete. Emerging evidence highlights the gut microbiome as a key factor linking metabolic dysfunction, immune activation, and neuronal damage. Even minor dysbiosis may interfere with microbial metabolite balance and disrupt intestinal integrity, leading to local and, consequently, systemic inflammation, which in turn drives altered pain response via the gut-brain-immune axis. Recent clinical and preclinical data show that reduced short-chain fatty acid availability, altered bile acid and tryptophan metabolism, let alone expansion of pro-inflammatory species collaboratively contribute to DN onset and progression. Moreover, advances in metagenomics and metabolomics reveal reproducible microbiome-derived biomarkers that could predict neuropathy risk and pain phenotypes independent of glycemic control, supporting the microbiome as both a mechanistic driver and a measurable potential diagnostic tool. In the context of management, microbiota-affected interventions, such as probiotics, synbiotics, omega-3 supplementation, and fecal microbiota transplantation, show early promise in alleviating symptoms and improving nerve function. This mini-review synthesizes current evidence on the microbiome's role in DN, emphasizing its dual potential as a biomarker for early diagnosis and a therapeutic target for precision microbiome-based interventions.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Diabetic Neuropathies/microbiology/therapy/metabolism
*Dysbiosis/microbiology
Animals
Probiotics/therapeutic use

@article {pmid41255078,
year = {2025},
author = {Ghoshal, UC and Ramakrishna, BS and Rathi, PM and Shukla, A and Panigrahi, MK and Jain, S and Saha, I and Chakravartty, K and Singh, M and Mustafa, U and Sahu, S and Ghoshal, U and Chandnani, S and Goenka, MK and Mitra, M},
title = {Probiotic Blend of Lactobacillus acidophilus LA-5 and Bifidobacterium animalis ssp. Lactis BB-12 in Non-constipated Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.},
journal = {Journal of gastroenterology and hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgh.70137},
pmid = {41255078},
issn = {1440-1746},
support = {//Zydus Healthcare Limited and Shanti Public Educational and Development Society/ ; },
abstract = {BACKGROUND: As dysregulated gut microbiota is known in irritable bowel syndrome (IBS) and probiotics may improve it, we investigated the efficacy and safety of a combination probiotic, Lactobacillus acidophilus LA-5 and Bifidobacterium animalis ssp. lactis BB-12 in non-constipated IBS.

METHODS: Two hundred non-constipated IBS patients were randomized to the above-mentioned probiotic and placebo for 84 days. The outcome measures included IBS-Global Improvement Scale (IBS-GIS), IBS-Quality of Life (IBS-QoL), EAR3Q, IBS-Severity Scoring System (IBS-SSS), and patient-reported improvement. Fecal microbiota was evaluated in a subset.

RESULTS: Response in IBS-GIS was higher with probiotics than with placebo at days 28 (19.3% vs. 8.9%; p = 0.048), 56, and 84. Total and abdominal pain, distension, and QoL scores of IBS-SSS decreased at day 28 with probiotics that persisted till days 56 and 84. The percentage of patients with "severe" symptoms reduced from 20.8% at baseline to 3.9% at day 84, and the median IBS-QoL score decreased significantly at day 28; the beneficial effect on QoL was sustained till days 56 and 84 (p < 0.001). Improvement in abdominal pain, distension, urgency of defecation, bowel habit satisfaction, and stool frequency was noted earlier with probiotics than with placebo; 4.0% in the probiotic group and 0.9% in the placebo group had mild/moderate adverse events (p = 0.167). Symptom recurrence occurred in 3.0% in the probiotic group and 3.9% in the placebo group during follow-up of 180 days (p = 0.718). No difference was observed in the fecal microbiota between the two groups, but healthy genera were enriched with probiotics.

CONCLUSIONS: The probiotic blend studied was more effective than placebo in non-constipated IBS in adults.},
}

@article {pmid41254951,
year = {2025},
author = {González-Correa, C and Miñano, S and Moleón, J and Toral, M and Robles-Vera, I and Sánchez, M and Jiménez, R and Olivares, M and Martín-Morales, N and O'Valle, F and Guerra-Hernández, E and Romero, M and Gómez-Guzmán, M and Duarte, J},
title = {The probiotic Limosilactobacillus fermentum CECT5716 enhances the antihypertensive response to hydrochlorothiazide in spontaneously hypertensive rats.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2586324},
doi = {10.1080/19490976.2025.2586324},
pmid = {41254951},
issn = {1949-0984},
mesh = {Animals ; Rats, Inbred SHR ; *Hydrochlorothiazide/pharmacology/administration & dosage/therapeutic use ; *Probiotics/administration & dosage/pharmacology ; *Hypertension/drug therapy/microbiology/physiopathology ; Gastrointestinal Microbiome/drug effects ; Rats ; *Antihypertensive Agents/pharmacology/administration & dosage/therapeutic use ; Male ; *Limosilactobacillus fermentum/physiology ; Blood Pressure/drug effects ; Fecal Microbiota Transplantation ; },
abstract = {Limosilactobacillus fermentum CECT5716 (LC40) consumption reduces hypertension and improves endothelial dysfunction in spontaneously hypertensive rats (SHRs). The diuretic hydrochlorothiazide (HCTZ) lowers blood pressure in SHR but disrupts the gut microbiota balance. In this study, we investigated whether the LC40 could enhance the antihypertensive effects of HCTZ. Interestingly, we found that coadministration of LC40 with HCTZ potentiated the beneficial effects of HCTZ on endothelial dysfunction and blood pressure without altering plasma HCTZ concentrations or exacerbating electrolyte imbalances. These protective effects were associated with normalization of microbiota alterations, including a reduction in the Firmicutes/Bacteroidota ratio, suppression of lipopolysaccharide biosynthesis, and an increase in acetate-producing bacteria. Additionally, LC40 reduced intestinal pathology and endotoxemia. Furthermore, the HCTZ + LC40-treated rats exhibited reduced neuroinflammation and sympathetic activity, along with an immunoregulatory effect characterized by increased regulatory T cell infiltration and a reduction of vascular oxidative stress in the aorta. The beneficial effects of LC40 in HCTZ-treated rats appeared to be microbiota dependent, as they were replicated through fecal microbiota transplantation in germ-depleted normotensive rats. Our findings identify the gut microbiota as a novel therapeutic target to enhance the antihypertensive effects of diuretics. The coadministration of LC40 with HCTZ modulates immune responses, providing a promising strategy to improve hypertension management.},
}

Animals
Rats, Inbred SHR
*Hydrochlorothiazide/pharmacology/administration & dosage/therapeutic use
*Probiotics/administration & dosage/pharmacology
*Hypertension/drug therapy/microbiology/physiopathology
Gastrointestinal Microbiome/drug effects
Rats
*Antihypertensive Agents/pharmacology/administration & dosage/therapeutic use
Male
*Limosilactobacillus fermentum/physiology
Blood Pressure/drug effects
Fecal Microbiota Transplantation

@article {pmid41253445,
year = {2025},
author = {Chen, YL and Meng, LL and Wu, JY and Yang, XY and Ouyang, L and Wu, BF and Xu, HX and Gu, JL and Wang, YL and Jing, XY and Lu, SF and Fu, SP},
title = {Electroacupuncture Reprograms Gut Microbiota and Confers Cerebral Protection After Stroke through Enhanced Regulatory T Cell Response.},
journal = {The American journal of Chinese medicine},
volume = {},
number = {},
pages = {1-24},
doi = {10.1142/S0192415X25500855},
pmid = {41253445},
issn = {1793-6853},
abstract = {Ischemic stroke seriously endangers both the health and quality of life of patients. The gut microbiota, which plays a crucial role in modulating communication between the gut and the nervous system, has emerged as a promising target for therapeutic interventions in stroke. Electroacupuncture (EA), which is associated with intestinal immunity, has been proven to exert significant beneficial effects in ischemic stroke, but its exact mechanism remains unclear. In this study, we investigated the regulatory mechanism of EA on the microbiome-gut-brain axis following ischemic stroke. In rat models of ischemic stroke, EA treatment significantly reduced cerebral infarct volume and neuronal damage following cerebral ischemia-reperfusion injury, and also modulated the composition, diversity, and taxonomic distribution of the gut microbiota. Fecal microbiota transplantation from EA-treated donors significantly reduced cerebral infarct volume and neuronal damage in the ischemic hemisphere of recipient mice, and likewise upregulated Treg cell expression to suppress immune-inflammatory responses in the brain. These results indicate that, through modulation of the gut microbiota, which in turn regulates Treg-mediated immune-inflammatory responses, EA ameliorates cerebral ischemic injury to thereby improve the prognosis of ischemic stroke patients. This study provides new perspectives on the efficacy of EA in the treatment of ischemic stroke.},
}

@article {pmid41253270,
year = {2025},
author = {Ding, L and Xu, JY and Zhang, LL and Liu, Y and Gu, KT and Liang, YZ and Hidayat, K and Wan, Z and Chen, GC and Qin, LQ},
title = {Lactoferrin alleviates non-alcoholic steatohepatitis via remodeling gut microbiota to regulate serotonin-related pathways.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.11.034},
pmid = {41253270},
issn = {2090-1224},
abstract = {INTRODUCTION: Lactoferrin (LF), a multifunctional glycoprotein, has been implicated in the regulation of glucose and lipid metabolism.

OBJECTIVES AND METHODS: This study employed in vivo and in vitro models to investigate the direct effects of LF on non-alcoholic steatohepatitis (NASH) and to elucidate its underlying mechanisms.

RESULTS: LF intervention alleviated hepatic lipid metabolic disorders and liver injury in high-fat, high-cholesterol cholate-containing diet (HFCCD)-fed mice by mitigating oxidative stress, suppressing the inflammatory cGAS/STING pathway, and reducing M1 proinflammatory macrophage polarization. These effects were validated in free fatty acid (FFA)-treated HepG2 cells and AML12 cells. Furthermore, LF ameliorated HFCCD-induced gut microbiota dysbiosis and increased short-chain fatty acid levels. The critical role of gut microbiota in mediating the hepatoprotective effects of LF was confirmed through antibiotic-induced microbiome depletion and fecal microbiota transplantation. Mechanistically, LF modulated gut-liver serotonin signaling and promoted fatty acid β-oxidation through the HTR2A-PPARα-CPT-1A pathway, an effect abolished by the HTR2A agonist DOI. In a co-culture system, LF treatment of the Caco-2/HT29 monolayer alleviated lipid accumulation and regulated the HTR2A-PPARα-CPT-1A pathway in FFA-treated HepG2 cells.

CONCLUSIONS: These findings indicate that LF attenuates NASH by remodeling gut microbiota to modulate microbiota-derived serotonin signaling and enhance fatty acid oxidation.},
}

@article {pmid41252333,
year = {2025},
author = {Bahji, A and Brietzke, E and Cooke, NCA and Clement, F and Frey, BN and Hofmeister, M and Kennedy, SH and Lam, R and Milev, R and Moinul, D and Parikh, SV and Patten, S and Ravindran, A and Rosenblat, JD and Samaan, Z and Schaffer, A and Saleem, A and Beaulieu, S and Tourjman, V and Van Ameringen, M and Vigod, S and Yatham, L and Taylor, V and , },
title = {The Canadian Network for Mood and Anxiety Treatments Task Force Recommendations for the Use of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplants in Adults With Major Depressive Disorder: Recommandations du Groupe de travail du Réseau canadien pour le traitement des troubles de l'humeur et de l'anxiété (Canadian Network for Mood and Anxiety Treatments, CANMAT) concernant l'utilisation des probiotiques, des prébiotiques, des symbiotiques et de la transplantation de microbiote fécal chez les adultes atteints de trouble dépressif majeur.},
journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie},
volume = {},
number = {},
pages = {7067437251394363},
doi = {10.1177/07067437251394363},
pmid = {41252333},
issn = {1497-0015},
abstract = {BackgroundApproximately one-third of adults with major depressive disorder (MDD) experience limited response or intolerable side effects with existing pharmacotherapies. As such, innovative treatments targeting novel biological pathways are under investigation. One promising area of research is the gut microbiome and its influence on mood through the microbiota-gut-brain axis. Clinical studies have begun evaluating microbiome-targeted interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) as potential treatments for MDD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to evaluate the evidence for microbiome-targeted interventions in adults with MDD and to provide updated clinical recommendations.MethodsA systematic review of randomized controlled trials (RCTs) and meta-analyses was conducted, assessing interventions such as probiotics, prebiotics, synbiotics, and FMT in adults with MDD. The CANMAT methodology was used to determine levels of evidence and treatment line recommendations, which were presented in a question-and-answer format.ResultsTwenty-three RCTs and eight meta-analyses were included. Probiotics have been the most extensively studied and have demonstrated modest improvements in depressive symptoms, particularly when used in an adjunctive manner. However, recent high-quality trials yielded mixed results. Evidence for prebiotics and FMT was limited and inconclusive, while synbiotics were assessed in only one small RCT. Most interventions were well tolerated, with few serious adverse events.ConclusionsProbiotics may be cautiously considered as third-line adjunctive treatments for MDD, though findings remain inconsistent. There is currently insufficient evidence to recommend prebiotics, synbiotics, or FMT in clinical practice. Further large-scale, well-controlled trials are needed to clarify efficacy, safety, and optimal patient subgroups.},
}

@article {pmid41252206,
year = {2025},
author = {Moreau, GB and Tian, J and Natale, NR and Naz, F and Young, MK and Nayak, U and Tanyüksel, M and Rigo, I and Madden, GR and Abhyankar, MM and Hagspiel, N and Brovero, S and Worthington, M and Behm, B and Marie, C and Petri, WA and Ramakrishnan, G},
title = {FMT promotes type 2 mucosal immune responses with colonic epithelium proliferation in recurrent CDI patients.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.195678},
pmid = {41252206},
issn = {2379-3708},
abstract = {BACKGROUND: Fecal Microbiota Transplantation (FMT) is the most effective therapy for recurrent Clostridioides difficile infection (rCDI), yet its mechanism of action remains poorly understood.

METHODS: We report the results of a clinical trial of subjects undergoing FMT therapy for rCDI (n=16), analyzing colon biopsies, plasma, peripheral blood mononuclear cells, and stool at the time of FMT and two-month follow-up. Plasma and colon biopsy samples were also collected from healthy controls for comparison with rCDI patients. Microbiome composition, colonic gene expression, and immune changes were evaluated through high-throughput sequencing and immunoprofiling via flow cytometry.

RESULTS: No subjects experienced recurrence at follow-up. FMT significantly altered the intestinal microbiome but had no significant impact on the systemic immune system. In contrast, FMT promoted broad changes in colonic transcriptional profiles compared to both pre-FMT and healthy control biopsies, inhibiting genes associated with pro-inflammatory signaling and upregulating type 2 immunity and proliferative pathways (Myc and mTORC1). FMT increased expression of IL-33 and the type 2 immune EGFR family ligand amphiregulin, potentially explaining upregulation of Myc and mTORC1 pathways. Spatial transcriptomics demonstrated that these changes were localized to the colonic epithelium. Comparison of transcriptional profiles with available single cell gene sets determined that post-FMT biopsies were enriched in signatures associated with proliferative cell types while repressing signatures of differentiated colonocytes.

CONCLUSIONS: We conclude that FMT promotes proliferation of the colonic epithelium in rCDI patients, which may drive regeneration and protect against subsequent CDI.

CLINICALTRIALS: gov NCT02797288.

FUNDING: NIH grants R01 AI152477, R01 AI124214, and K23 AI163368.},
}

@article {pmid41250648,
year = {2025},
author = {Yang, J and Tan, H and Peng, X and Nie, S},
title = {Tamarind Seed-Derived Xyloglucan Attenuates Insulin Resistance in Mice through Gut Microbiota.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c07829},
pmid = {41250648},
issn = {1520-5118},
abstract = {Xyloglucan (XG), a plant polysaccharide abundant in tamarind seeds, is FDA-approved for use as a food additive, stabilizer, thickener, or gelling agent. While its structural properties have been well-studied, its physiological effects remain unclear. This study employed a high-fat diet-induced insulin resistance mouse model to evaluate the effects of XG on metabolic disturbances, combining 16S rRNA sequencing and metabolomics to determine the role of gut microbiota. Results showed that XG intervention in HFD-fed mice improved glucose tolerance and liver function and reduced inflammation and oxidative stress, linked to altered carnitine and tryptophan metabolism. Gut microbiota analysis revealed selective enrichment of Bifidobacterium. Crucially, the benefit of XG was transferable via fecal microbiota transplantation but was abolished by antibiotic-induced microbiota depletion. This study demonstrates that tamarind seed-derived xyloglucan alleviates metabolic disturbances via a gut-microbiota-dependent mechanism, supporting its potential probiotic role in functional foods.},
}

@article {pmid41250124,
year = {2025},
author = {Huang, SW and Lin, CR and Chang, YH and Ni, YH and Chen, HL and Liu, HH},
title = {Cross-country multi-modal evidence links Aspergillus to biliary atresia.},
journal = {Gut pathogens},
volume = {17},
number = {1},
pages = {94},
pmid = {41250124},
issn = {1757-4749},
abstract = {BACKGROUND: Biliary atresia (BA) is the leading cause of pediatric liver transplantation. It is characterized by progressive extrahepatic bile duct obstruction in young infants. Inspired by the success of antifungal treatment in a newborn with BA-related obstructive cholangitis, we explored a potential link between BA and fungi, particularly Aspergillus. Fecal DNA was analyzed using 18S ribosomal sequencing and validated with a published fecal metagenomic dataset. Epidemiological data from the UK, Taiwan, and Japan were also examined.

RESULTS: Gut Aspergillus was exclusively detected in BA cases, suggesting it may be a potential trigger. Independent fecal metagenomic data from China and epidemiological correlations further supported this hypothesis. In the UK, BA presentations strongly correlated (r = 0.98, 95% CI [0.36, 1.0], p = 0.02) with Aspergillosis, but not with Candidiasis, during the COVID-19 lockdown. In Taiwan, a decade of data showed BA incidence was significantly associated (r = 0.78, 95% CI [0.29, 0.94], p = 0.01) with yearly Aspergillus-positive isolates among cancer-adjusted hospital admissions. In Japan, BA cases over 25 years correlated significantly (r = 0.85, 95% CI [0.37, 0.97], p = 0.01) with visceral Aspergillus burdens in autopsied cases, but not with other fungal infections.

CONCLUSIONS: The resolution of obstructive cholangitis in the antifungal-treated index case, together with multi-modal, cross-country evidence, highlights a potential link between gut Aspergillus and BA. Although limited by small sample size, retrospective design, and lack of mechanistic validation, the study may still be interpreted as hypothesis-generating and underscores the need for prospective studies to validate and extend these observations.},
}

@article {pmid41249722,
year = {2025},
author = {Xu, N and He, Y and Yang, G and Huang, X},
title = {Exploring the Role of Gut Microbiota in Chronic Spontaneous Urticaria: Mechanisms and Potential Therapeutic Implications.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {41249722},
issn = {1867-1314},
support = {no. 82103751//National Natural Science Foundation of China/ ; },
abstract = {Gut microbiota dysbiosis has emerged as a significant factor in the pathogenesis of chronic spontaneous urticaria (CSU), a condition characterized by immune dysregulation and skin inflammation. This review summarizes the current understanding of the role of gut microbiota in CSU pathogenesis, highlighting the alterations in microbial composition and function, the mechanisms by which dysbiosis triggers systemic inflammation and skin mast cell activation, and the impact of microbial metabolites. We critically evaluate the potential of gut microbiota-targeted therapies, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), as novel treatment strategies for CSU. Despite the evident promise of these approaches, significant challenges persist, including the necessity for personalized interventions, the collection of long-term efficacy and safety data, and a more profound understanding of the complex interplay between the gut and skin. Future research endeavors must prioritize the execution of clinical trials that evaluate the efficacy of gut microbiota modulation in CSU patients and the identification of biomarkers that can effectively predict treatment response.},
}

@article {pmid41248567,
year = {2025},
author = {Huang, F and Zhang, L and Cheng, S and Zhang, Z and Xiang, Q and Xiao, Z},
title = {Banxia Baizhu Tianma Decoction improves posterior circulation ischemia vertigo in rats via gut microbiota and TLR4-NF-κB-MyD88 pathway.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157539},
doi = {10.1016/j.phymed.2025.157539},
pmid = {41248567},
issn = {1618-095X},
abstract = {BACKGROUND: Posterior circulation ischemia vertigo (PCIV) frequently presents with vestibular dysfunction in patients suffering from posterior circulation stroke. The conventional approaches often fail to address PCIV's complex pathophysiology, which involves neuroimmune dysregulation, hemodynamic abnormalities, and gut-brain axis disruption. Banxia Baizhu Tianma Decoction (BBTD), a traditional Chinese medicine, is employed in treating PCIV and vasogenic vertigo, but the mechanisms underlying its efficacy require further elucidation.

PURPOSE: This study examines the therapeutic mechanisms and efficacy of BBTD for PCIV, particularly focusing on its impacts on neuroinflammation, gut microbiota communities, and gut barrier using a rat model of PCIV.

METHODS: The chemical and bioactive constituents of BBTD were profiled using ULPLC-Q Exactive-Orbitrap-MS. The PCIV model was employed and treated with BBTD for 7 days. Neurological score was measured with balance beam test; cerebellar pathology was assessed by H&E and Nissl staining. The TTC staining was used to measure cerebral infarct volume. The levels of IL-6, IL-1β, and TNF-α in serum and cerebellar tissue was analyzed by ELISA. Its mechanisms were investigated by 16S rRNA sequencing, antibiotic antagonistic and fecal microbiota transplantation (FMT) experiments. Significant alterations in gut microbiota and their detailed mechanisms were identified. Intestinal barrier integrity was assessed by AB-PAS staining, tight junction proteins (MUC2, occludin, claudin-1, ZO-1), and colonic inflammatory cytokine levels. The levels of short-chain fatty acids in the cecal contents and cerebellar tissues of our experimental rats using gas chromatography-mass spectrometry (GC-MS).

RESULTS: Our findings demonstrated that BBTD significantly improved neurological function, ameliorates cerebral ischemia, and alleviated neuroinflammation in rats. Moreover, BBTD significantly modulated the diversity and composition of the gut microbiota, elevating Lactobacillus and Akkermansia, while reducing Clostridiales and Ruminococcaceae. The further antibiotic depletion and FMT experiments confirmed that gut microbiota was essential for BBTD-induced neuroinflammation and gut barrier protection in PCIV. BBTD ameliorated intestinal damage by enhancing acidic mucins and tight junction protein expression. BBTD treatment markedly increased the concentrations of propionic acid in intestinal fecal content and cerebellar tissue. Mechanistically, BBTD ameliorates ischemia-induced neuroinflammation and neuronal injury by modulating the TLR4-NF-κB-MyD88 pathway via the gut-brain axis.

CONCLUSION: BBTD ameliorates PCIV through gut-brain axis modulation, restoring gut barrier-microbiota balance and suppressing TLR4-NF-κB-MyD88 signaling. BBTD treatment and FMT may serve as an effective therapeutic strategy for mitigating posterior circulation ischemia progression.},
}

@article {pmid41247394,
year = {2025},
author = {Wu, Y and Chan, SSM and Leung, PWL and Lo, HHL and Ho, SWS and Mo, FYM and Ho, CSW and Shea, CKS and Su, Q and Leung, TF and Chan, FKL and Ng, SC and Wong, OWH},
title = {The Mediating Role of Eating Behaviors Between Autistic Symptoms and Dietary Issues Among Chinese Children With Autism.},
journal = {Journal of autism and developmental disorders},
volume = {},
number = {},
pages = {},
pmid = {41247394},
issn = {1573-3432},
support = {InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China//InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China/ ; InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China//InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China/ ; The D.H. Chen Foundation//The D.H. Chen Foundation/ ; The D.H. Chen Foundation//The D.H. Chen Foundation/ ; PF22-77807//The Hong Kong PhD Fellowship Scheme/ ; },
abstract = {PURPOSE: Eating and dietary challenges are common among children with autism, but their associations with clinical symptoms remain unclear. This study aims to describe dietary issues, including nutritional problems and overexposures to food additives in autistic children, and their associations with clinical symptoms.

METHODS: This case-control study involved 836 children (469 with autism and 367 without autism; mean age = 8.3 years) profiled on autistic symptoms, eating behaviors, and dietary patterns with parent-reported questionnaires. Nutritional insufficiencies, dietary quality and food additives exposures were compared using regression models adjusted for age and sex. Multivariate logistics or linear regression models were used to identify clinical symptoms that predict dietary issues, with mediation analyses examining eating behaviors' roles.

RESULTS: Autistic children had lower protein intake, more vitamin and mineral insufficiencies, higher exposure to food additives, and poorer diet quality. They consumed fewer fruits/vegetables and more animal-based fats, with 38.2% exceeding 125% of the Estimated Energy Requirement (vs. 22.9% controls), suggesting energy-dense, ultra-processed food preferences. Diminished food enjoyment and increased food fussiness mediated between low social motivation and nutritional insufficiencies, as well as poorer diet quality. Further, difficulties with food responsiveness and emotional eating patterns mediated between more restricted and repetitive behaviors and higher exposures to emulsifiers/thickeners.

CONCLUSION: Autistic children, especially those with severe core symptoms, are susceptible to multifaceted dietary issues such as preference for low-quality food and nutrient deficiencies. It is crucial to implement personalized treatment strategies that target their specific eating behaviors to effectively address dietary challenges.},
}

@article {pmid41247324,
year = {2025},
author = {Weagley, JS and Cárdenas, LAC and Romani, A and Sullender, ME and Aggarwal, S and Makimaa, H and Hogarty, MP and Rodgers, R and Kennedy, EA and Foster, L and Schriefer, LA and Baldridge, MT},
title = {Differential Microbial Community Assembly Following Co-housing versus Microbiota Transplant.},
journal = {The ISME journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/ismejo/wraf256},
pmid = {41247324},
issn = {1751-7370},
abstract = {Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transfer of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of faecal or caecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, faecal transplantation, and caecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored bacterial and viral populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transfer-recipient control mice. Although all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. Overall, faecal and caecal transplant resulted in highly similar colonization processes with some minor variation in enrichment for two specific bacterial families. This study provides valuable insights into microbial ecology, as well as the dynamics underlying experimental microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transfer in mouse models.},
}

@article {pmid41247039,
year = {2025},
author = {Kelly, CR and Feuerstadt, P},
title = {Diagnosis and Management of C. difficile.},
journal = {The American journal of gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000003844},
pmid = {41247039},
issn = {1572-0241},
abstract = {Clostridioides difficile infection (CDI) is challenging to diagnose and treat. Recently published studies and clinical observations have improved our understanding around diagnostic testing and positioning of antibiotics and microbiota-based therapies. This review synthesizes current evidence and guidelines on CDI diagnosis, highlighting the limitations of individual tests and the value of algorithmic approaches. Treatment paradigms are discussed across the spectrum of disease severity, with vancomycin and fidaxomicin as first-line therapies and the diminishing role of metronidazole. For recurrent CDI, newer fecal microbiota-based therapies, including Fecal Microbiota, live-jslm (Rebyota, RBL) and Fecal Microbiota Spores, live-brpk (Vowst, VOS), are reviewed. The role of conventional fecal microbiota transplantation (FMT), particularly in fulminant CDI, is also addressed, including challenges resulting from FDA policies around stool bank material. We aim to clarify diagnostic and therapeutic approaches and optimize care for patients with CDI.},
}

@article {pmid41246810,
year = {2025},
author = {Tan, H and Chen, M and Yao, H and Li, S and Nie, S},
title = {Dominant Gut Commensals Enriched by Pectin with Low Esterification Degree Orchestrate the Amelioration of Acute Ulcerative Colitis.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c09097},
pmid = {41246810},
issn = {1520-5118},
abstract = {Dietary fiber's health benefits are increasingly recognized as microbiota-dependent, with effects influenced by fiber structure. We previously observed that low-esterified pectin provides superior protection against DSS-induced colitis compared to its high-esterified form, but the mechanism was unknown. This study investigated the microbiota-dependent pathway underlying low-esterified pectin's anticolitic effect using FMT. By evaluating three pectin-induced bacteria (Bifidobacterium longum NSP002, Bacteroides xylanisolvens NSP003, Enterococcus faecium NSP004) individually and in a consortium, we found that the consortium exerted a significantly stronger protective effect, suggesting synergistic interactions and highlighting its potential as an FMT alternative. Mechanistically, this protection may involve three axes: (1) Gut microbiome remodeling (reduced Akkermansia, increased Bacteroides, elevated propionic acid). (2) Intestinal homeostasis modulation (reduced mme/calprotectin expression, activated PI3K/calcium signaling). and (3) Systemic metabolic reprogramming (increased serum phenylethylamine, enriched phenylalanine metabolism). These findings support the clinical potential of pectin for optimizing enteral nutrition and using pectin-enriched microbiota consortia to target IBD pathogenesis.},
}

@article {pmid41246285,
year = {2025},
author = {Ahmed, N and Gaur, V and Kamle, M and Chauhan, A and Chauhan, R and Kumar, P and Singh, NA},
title = {Microbiome-based therapeutics for metabolic disorders: harnessing microbial intrusions for treatment.},
journal = {Frontiers in medical technology},
volume = {7},
number = {},
pages = {1695329},
doi = {10.3389/fmedt.2025.1695329},
pmid = {41246285},
issn = {2673-3129},
abstract = {The rising global rates of metabolic disorders, such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, and metabolic syndrome, call for new treatment methods beyond traditional drugs. The human gut microbiota, made up of trillions of microorganisms that plays a crucial role in maintaining metabolic balance through complex biochemical processes and interactions between hosts and microbes. Dysbiosis, which involves changes in microbial composition and a decrease in diversity, has become a major factor in metabolic problems. This disruption impacts the production of short-chain fatty acid, increase in permeability of intestine, and causes enduring low-grade inflammation. This review features into the potential of treatments based on microbiome for metabolic syndromes, focusing on probiotics, prebiotics, synbiotics, and postbiotics. It also encompasses innovative methods such as engineered microbial consortium, fecal microbiota transplantation (FMT), and vaginal microbiota transplantation (VMT). Probiotics show significant promise in improving blood sugar control and enhancing lipid levels. Prebiotics help bring about positive changes in microbial composition and the production of beneficial metabolites. Synbiotic combinations provide added benefits by helping good microbes thrive while supplying nutrients they can ferment. Postbiotics have recent research focus because they are safer, more stable, easier to store, and less likely to contribute to antibiotic resistance comparative to live probiotics. Even now there are substantial complications in translating microbiome research into standardized therapeutics despite of promising pre-clinical outcomes and some initial clinical data. These comprises individual variances, strain-specificity, dosage problems, regulation issues, and the necessity for personalised treatment strategies. Future success will depend upon personalized medicine, technological developments, and the incorporation of multi-omics strategy to generate metabolic health therapeutics depending on targeted microbiomes.},
}

@article {pmid41245267,
year = {2025},
author = {Makkar, SK and Bishnupuri, KS},
title = {The gut microbiome and gastrointestinal cancers: mechanisms, biomarkers and therapeutic opportunities.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1676796},
doi = {10.3389/fphys.2025.1676796},
pmid = {41245267},
issn = {1664-042X},
abstract = {Gastrointestinal (GI) cancers remain a leading global cause of cancer-related mortality, significantly impacting public health and healthcare systems worldwide. Emerging evidence underscores the critical role of gut microbiome dysbiosis-characterized by disrupted microbial diversity and function-in GI carcinogenesis. Utilizing recent advancements in multi-omics technologies and sophisticated computational biology, researchers have elucidated distinct microbial signatures associated with colorectal, gastric, hepatobiliary, pancreatic, and esophageal cancers. This review comprehensively analyzes the primary mechanisms through which gut microbes contribute to cancer development and progression, encompassing genotoxicity, chronic inflammation, metabolic dysregulation, epigenetic modifications, and immunomodulation. Moreover, we explore innovative microbiome-derived biomarkers for potential clinical applications, including early diagnosis, prognosis assessment, and therapeutic response prediction. The intricate interactions between microbiota and standard cancer therapies-chemotherapy, immunotherapy, and radiation therapy-are discussed, highlighting microbiome influences on therapeutic efficacy and adverse effect profiles. We also critically assess the impact of modifiable factors such as diet, medications, lifestyle, and environmental exposures on microbiome composition and cancer risk. The review evaluates emerging therapeutic interventions, including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation (FMT), and engineered live biotherapeutics. Despite notable advancements, significant hurdles remain, including clarifying causality, methodological standardization, and equitable global research representation. Addressing these challenges, we propose a strategic research agenda aimed at harnessing microbiome insights to advance precision oncology and improve GI cancer outcomes globally.},
}

@article {pmid41244880,
year = {2025},
author = {Bautista, J and Hidalgo-Tinoco, C and Di Capua Delgado, M and Viteri-Recalde, J and Guerra-Guerrero, A and López-Cortés, A},
title = {The gut-brain-circadian axis in anxiety and depression: a critical review.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1697200},
doi = {10.3389/fpsyt.2025.1697200},
pmid = {41244880},
issn = {1664-0640},
abstract = {Anxiety and depressive disorders rank among the most prevalent psychiatric conditions worldwide, yet remission rates remain unsatisfactory despite advances in pharmacological and psychotherapeutic interventions. The gut-brain axis has emerged as a transformative framework for understanding these disorders, emphasizing bidirectional communication between the central nervous system, the enteric nervous system, the endocrine and immune systems, and the gut microbiota. Preclinical studies demonstrate that germ-free or dysbiotic states exaggerate hypothalamic-pituitary-adrenal (HPA) reactivity, remodel synaptic plasticity, and induce anxiety- and depression-like behaviors, while fecal microbiota transplantation confirms the causal influence of microbial communities. Mechanistically, neural (e.g., vagal), endocrine (e.g., cortisol), immune (e.g., cytokine), and metabolic (e.g., short-chain fatty acids, tryptophan metabolites, bile acids) pathways converge to regulate mood and stress resilience. An underappreciated yet critical dimension of this model is circadian rhythmicity. Both host endocrine cycles and microbial communities exhibit diurnal oscillations that synchronize metabolism, immune activity, and neural signaling. Disruption of these rhythms, through factors such as sleep disturbance, irregular feeding, or shift work, alters microbial diversity, dampens metabolite oscillations, destabilizes HPA regulation, and enhances neuroinflammation, thereby amplifying vulnerability to psychiatric disorders. Collectively, evidence supports a model in which anxiety and depression are systemic conditions arising from integrated neural, immune, endocrine, metabolic, and circadian dysregulation, rather than isolated brain-based pathologies. This reconceptualization positions microbial taxa and metabolites as candidate biomarkers and therapeutic targets. Precision interventions, ranging from diet and psychobiotics to fecal microbiota transplantation, chrononutrition, and immune-modulatory strategies, offer promising avenues for personalized psychiatry.},
}

@article {pmid41244772,
year = {2025},
author = {Li, Q and Song, XC and Li, K and Wang, J},
title = {Gut-lung immunometabolic crosstalk in sepsis: from microbiota to respiratory failure.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1685044},
doi = {10.3389/fmed.2025.1685044},
pmid = {41244772},
issn = {2296-858X},
abstract = {Sepsis is a systemic immune-metabolic disorder syndrome caused by infection, in which gut microbiota dysbiosis plays a central role in the occurrence and development of multi-organ dysfunction. This paper systematically elaborates on the bidirectional regulatory mechanism of the "gut-lung axis" in sepsis. Gut microbiota dysregulation damages the gut barrier function, reduces the production of short-chain fatty acids (SCFAs), and increases endotoxin translocation. Subsequently, it activates alveolar macrophage polarization, promotes the formation of neutrophil extracellular traps (NETs), and leads to an imbalance in the Treg/Th17 cell ratio, ultimately exacerbating the pathological process of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Conversely, the pulmonary inflammatory response can also aggravate gut barrier damage through circulating inflammatory mediators, forming a vicious cycle. Mechanistically, HIF-1α, mTOR, and Sirtuins do not act in isolation. Instead, they jointly regulate the metabolic fate of immune cells through spatiotemporally dynamic interactions. During the evolution of sepsis, these signals exhibit opposite regulatory polarities during the hyper-inflammatory phase and the immunosuppressive phase, and mitochondrial dysfunction and oxidative stress further amplify the inflammatory cascade reaction. Preclinical research evidence shows that microbiota-based intervention measures (including probiotic preparations, fecal microbiota transplantation, and SCFA supplementation) and vagus nerve electrical stimulation can effectively alleviate sepsis-related lung injury and improve prognosis, but there is significant individual heterogeneity in their therapeutic effects. Future research should not be restricted to descriptive associations. Instead, it is essential to conduct in-depth analyses of the specific logic of the aforementioned signaling networks in terms of cell types, subcellular compartments, and disease course timings, and clarify their context-dependent controversies to promote the transformation of mechanistic understanding into precision treatment. Meanwhile, research efforts should focus on constructing a multi-omics dynamic biomarker system integrating metagenomics, metabolomics, and immunophenotyping analysis and designing clinical trials through precise patient stratification to facilitate the clinical translation of individualized treatment strategies based on gut-lung axis regulation.},
}

@article {pmid41243436,
year = {2025},
author = {Cen, Q and Cui, Y and Jin, J and Feng, J and Xin, Y and Zhang, Z and Li, J and Wang, J and Zhang, A},
title = {Unraveling multiple sclerosis: a hidden interaction between intestinal microbiota and host lipid metabolism.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2576657},
doi = {10.1080/19490976.2025.2576657},
pmid = {41243436},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Multiple Sclerosis/metabolism/microbiology/therapy ; *Lipid Metabolism ; Animals ; },
abstract = {Dysregulation of the structure of the gut microbiota is closely linked to the risk of onset and progression of multiple sclerosis. The intricate interaction between the gut microbiota and lipid metabolism likely serves as a crucial pathway mediating this relationship: the gut microbiota directly or indirectly modifies lipid metabolism (including cholesterol, sphingolipids, phospholipids, and fatty acids) by controlling the production of specific metabolites (such as short-chain fatty acids, tryptophan metabolites, bile acids, trimethylamine-N-oxide, and lipopolysaccharides), thereby impacting core pathological processes in multiple sclerosis. Therefore, elucidating the specific roles and mechanisms of the gut microbiota in modulating lipid metabolism in multiple sclerosis will accelerate the development of precision therapeutic strategies. In this review, we conduct an in-depth exploration of the interaction between the gut microbiota and lipid metabolism in the context of multiple sclerosis and provide a comprehensive summary of existing strategies targeting the gut microbiota and lipid metabolism for treating multiple sclerosis (including microbiota-based therapies, pharmacotherapy, and lifestyle modifications). Finally, we outline the present challenges in this field and offer an in-depth prospect for future directions.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Multiple Sclerosis/metabolism/microbiology/therapy
*Lipid Metabolism
Animals

@article {pmid41243097,
year = {2025},
author = {Hang, WJ and Yin, R and Kang, XW and He, L and Cao, X and Chen, J},
title = {Berberine ameliorates high-fat diet-induced metabolic disorders through promoting gut Akkermansia and modulating bile acid metabolism.},
journal = {Chinese medicine},
volume = {20},
number = {1},
pages = {190},
pmid = {41243097},
issn = {1749-8546},
support = {82100402//National Natural Science Foundation of China/ ; 82370837//National Natural Science Foundation of China/ ; 2022CFB201//Bureau of Science and Technology of Hubei Province/ ; 2022YFE0209900//National Key Research and Development Program of China/ ; WZ21A02//Wuhan Municipal Health Commission's Scientific Research/ ; },
abstract = {BACKGROUND: Coptidis Rhizoma, the rhizome of Coptis chinensis Franch., has long been employed in the treatment of diabetes. Its active component, berberine, has been utilized in clinical practice; however, the underlying mechanisms of its protective effects remain to be fully elucidated.

METHODS: Metabolomics and lipidomics analyzed plasma metabolite and lipid changes in mice fed a high-fat diet and treated with 25 mg/kg/day berberine for three months. Metagenomics and microbiota transplantation identified gut microbiota responding to berberine. Co-administration of berberine and Akkermansia was studied for metabolic effects, analyzing plasma and fecal metabolomics.

RESULTS: Berberine reduced triglycerides and cholesterol, showing metabolic protective effects. Metagenomics identified Akkermansia as key to berberine's benefits, validated by microbiota transplantation. Berberine enhanced Akkermansia growth, preserving intestinal mucus and tight junctions. It promotes the conversion of cholesterol to bile acids by inhibiting adenosine 5 '-monophosphate -activated protein kinase (AMPK), which promotes the expression of cholesterol 7-alpha hydroxylase (CYP7A1). Co-administration of berberine and Akkermansia amplified these effects. Potential metabolites, including linoleic acid and N-acetylputrescine, contributed to the observed benefits.

CONCLUSION: Berberine, through Akkermansia, maintains intestinal integrity and reduces cholesterol, highlighting its potential as a therapeutic agent for metabolic disorders. Combining berberine with Akkermansia enhances its efficacy against hyperlipidemia.},
}

@article {pmid41242566,
year = {2025},
author = {Yousefi-Hashemabad, MJ and Hosseini Kakroudi, M and Pourashory, M and Forouzan, K and Yazdanpanah, N and Saleki, K and Rezaei, N},
title = {Intratumoral Bacterial Microbiota in Gastrointestinal Adenocarcinoma: From Computational Insights to Clinical Practice.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {108174},
doi = {10.1016/j.micpath.2025.108174},
pmid = {41242566},
issn = {1096-1208},
abstract = {Intratumoral microbiota refers to bacteria and other organisms residing within the tumor microenvironment and are intriguingly found throughout the TME, including in cancer cells, immune cells, and stromal components. Among these microbiota, bacteria have gained attention due to their emerging roles in tumor biology. Recent research has uncovered new pathophysiological and therapeutic roles for targeting intratumoral bacterial microbiota. Emerging evidence pointed out that certain taxa, including Fusobacterium nucleatum and Porphyromonas gingivalis, can drive tumorigenic activity, whereas taxa such as Lactobacillus spp. may act as a protective agent. Overall, bacteria can influence cancer progression through mechanisms including immune modulation, metabolic reprogramming, and genomic instability. Furthermore, advances in artificial intelligence (AI) and microbiome profiling have identified prognostic microbial signatures and markers of treatment response. In addition, the mediation of the tumor microbiota via probiotics, antibiotics, engineered microbes, and fecal transplants exhibits novel approaches in targeted cancer therapy. The present review captures the role of intratumoral bacterial microbiota in adenocarcinomas and their significance in cancer development and progression as evidenced by experimental and clinical research.},
}

@article {pmid41241915,
year = {2025},
author = {Preetham, K and Chatterjee, J},
title = {Research trend on the emerging role of the microbiome in idiopathic male infertility.},
journal = {Antonie van Leeuwenhoek},
volume = {118},
number = {12},
pages = {193},
pmid = {41241915},
issn = {1572-9699},
mesh = {Male ; Humans ; *Infertility, Male/microbiology/etiology ; *Microbiota ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; Oxidative Stress ; },
abstract = {Idiopathic male infertility remains a major challenge in reproductive medicine despite extensive diagnostic workups, prompting research into novel etiologies and interventions. Emerging evidence highlights the microbiome's role in modulating male reproductive health. This study analyzes global research trends on idiopathic male infertility and associated microbial health over the past two decades using a structured bibliometric approach. Data extracted from Scopus were examined through Biblioshiny and VOSviewer. The analysis reveals a clear transition from traditional genetic and oxidative stress-based studies to microbiome-centered and multi-omics investigations. Increased Research output and citation rates in recent years, underscoring the growing relevance of microbiome studies. Key contributors like Agarwal A, Wang X, Zhang H, and Lundy SD advanced understanding from genetic and oxidative causes to gut-testis and semen microbiome interactions. Leading contributors and countries, particularly China and the USA dominate collaborative networks. Key themes link microbial dysbiosis, oxidative stress, inflammation, and hormonal imbalance with impaired spermatogenesis. Environmental and lifestyle factors, including diet, alcohol, antibiotics, endocrine disruptors, and microplastics, were increasingly recognized as influencing microbiome-mediated fertility. Mechanistic insights into the gut-testis axis, endotoxemia, immune modulation, and nutrient metabolism suggest avenues for diagnostics and microbiome-based interventions, including probiotics, nutritional modulation, and fecal microbiota transplantation.},
}

Male
Humans
*Infertility, Male/microbiology/etiology
*Microbiota
Dysbiosis/microbiology
*Gastrointestinal Microbiome
Oxidative Stress

@article {pmid41241335,
year = {2025},
author = {Xu, Y and Ni, Y and Zhou, M and Gou, X},
title = {Qushi Huayu decoction alleviates NAFLD in mice by regulating gut microbiota homeostasis in the gut-liver axis via the pregnane X receptor.},
journal = {European journal of pharmacology},
volume = {1008},
number = {},
pages = {178366},
doi = {10.1016/j.ejphar.2025.178366},
pmid = {41241335},
issn = {1879-0712},
abstract = {BACKGROUND: Qushi Huayu decoction (QHD) is a traditional Chinese medicine formula with clinical experience in the treatment of non-alcoholic fatty liver disease (NAFLD). The gut-liver axis is directly connected via the portal vein, making gut microbiota dysbiosis and endotoxin circulation key drivers in the development and progression of NAFLD. However, the regulation of the gut-liver axis by QHD in NAFLD remains unreported, and its target mechanisms have yet to be elucidated.

MATERIALS AND METHODS: NAFLD was induced in male C57BL/6J mice via high-fat diet feeding, followed by 4 weeks of QHD administration. Comprehensive evaluation included serum biochemical analysis, liver histopathology examination, and quantification of proinflammatory enzyme activity. Mechanism studies were conducted via 16S rRNA sequencing, transcriptomics analysis, SCFAs analysis, RT-qPCR, Western blotting and ELISA techniques.

RESULTS: QHD therapy effectively ameliorates hepatic steatosis and lipid accumulation in a mouse model of NAFLD. In addition, QHD significantly increases intestinal tight junction proteins, thereby restoring intestinal barrier integrity and alleviating inflammatory responses. Transcriptomics revealed that QHD regulates multiple biological functions through multiple genes, in which inflammatory responses may play a key role. Simultaneously, QHD exerts beneficial modulation of the gut microbiota, increasing beneficial bacteria, particularly Akkermansia, while decreasing the prevalence of harmful microorganisms, such as Desulfovibrio. Fecal microbiota transplantation experiments demonstrates that gut microbiota remodeling partially mediates pharmacological efficacy of QHD against NAFLD. Notably, subsequent investigations identified that QHD altered the composition of the gut microbiota and the levels of acetic acid, propionic acid, and valeric acid in SCFAs in a PXR-dependent manner.

CONCLUSIONS: QHD exerts therapeutic effects on NAFLD by regulating the gut-liver axis. The mechanism by which QHD intervention ameliorates gut microbiota dysbiosis in NAFLD mice is associated with its regulation of PXR. This provides further scientific evidence and support for QHD's efficacy in improving NAFLD.},
}

@article {pmid41239321,
year = {2025},
author = {Alkuwaiti, SH and Skrabulyte-Barbulescu, J and Yassin, LK and Almazrouei, S and Aldhaheri, D and Alderei, M and BaniYas, S and Alshamsi, SH and Alnuaimi, A and Saeed, S and Alawadhi, M and Rutkowska-Gauvry, P and Ismail, FY and Hamad, MIK},
title = {Harnessing the microbiota-gut-brain axis to prevent and treat pediatric neurodevelopmental disorders: translational insights and strategies.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1286},
pmid = {41239321},
issn = {1479-5876},
abstract = {BACKGROUND: Pediatric neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), Rett syndrome (RTT), Tourette syndrome (TS), Down syndrome (DS), Fragile X syndrome (FXS), Prader–Willi syndrome (PWS), fetal alcohol spectrum disorder (FASD), pediatric epilepsy, congenital Zika syndrome (CZS), Wilson’s disease (WD), and cerebral palsy (CP), are associated with long-term impairments and high societal burden. Emerging evidence implicates the microbiota–gut–brain axis (MGBA) in early neurodevelopment with factors, such as maternal microbiota, birth mode, antibiotics, and infant diet shaping microbial colonization and influencing developmental outcomes.

OBJECTIVE: This review aims to synthesize current translational evidence from animal and human studies to address the following research questions: (1) How do disruptions in the MGBA contribute to the pathophysiology of pediatric neurodevelopmental disorders? (2) What microbiome alterations are consistently associated with these conditions? and (3) What ethical and safety considerations should be addressed in implementing early-life microbiome-based interventions? We also assess emerging microbiota-based interventions, including probiotics, prebiotics, dietary strategies, fecal microbiota transplantation, and traditional therapies, and their potential to modulate disease outcomes.

CONCLUSION: The MGBA presents a promising, yet currently preliminary, target for early intervention in pediatric neurodevelopmental disorders. There is emerging evidence that therapies targeting the microbiota could have an effect on neurodevelopment and outcomes of health and disease; however, most of the findings are in the initial stages, and the evidence is still inconsistent. Therefore, the findings must be translated into mechanisms of action over extended periods with longitudinal multi-omic studies to identify possible intervention windows, optimize personalized therapies, and evaluate the safety and efficacy of interventions targeting the microbiome. Till that point, these microbiota-targeted approaches should be approached cautiously and treated as experimental in the realm of pediatric interventions, given the present-day state of evidence.},
}

@article {pmid41241180,
year = {2025},
author = {Han, H and Park, J and Zhang, R and Subramaniyam, N and Das, S and Ge, X and Babu Komakula, SS and Wang, C and Desert, R and Chen, W and Song, Z and Athavale, D and Anwar, A and Lantvit, D and Guzman, G and Frutos, MD and Ramos-Molina, B and Nieto, N},
title = {INTESTINAL EPITHELIAL CELL-DERIVED OSTEOPONTIN PROTECTS AGAINST METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS BY MODULATING BILE ACID COMPOSITION AND THE GUT MICROBIOME.},
journal = {Cellular and molecular gastroenterology and hepatology},
volume = {},
number = {},
pages = {101678},
doi = {10.1016/j.jcmgh.2025.101678},
pmid = {41241180},
issn = {2352-345X},
abstract = {BACKGROUND & AIMS: The gut-liver axis plays a critical role in metabolic dysfunction‒associated steatohepatitis (MASH). Osteopontin (OPN, encoded by SPP1) is implicated in chronic liver disease; however, its expression in intestinal epithelial cells (IECs) and role in MASH remain unclear.

METHODS: We evaluated intestinal OPN expression during MASH progression in patients. To determine the function of IEC-derived OPN, we generated Spp1 knock-in (Spp1[KI IEC]) and knock-out (Spp1[ΔIEC]) mice and fed them a high-fat, high-fructose, high-cholesterol diet to induce MASH.

RESULTS: IEC OPN expression decreased with MASH progression and was inversely associated with liver injury. Loss of Spp1 in IECs exacerbated MASH, whereas overexpression or oral OPN administration was protective. Spp1[ΔIEC] mice exhibited increased hepatic inflammation, disrupted IEC morphology, elevated IEC apoptosis, reduced epithelial cell turnover, and heightened intestinal permeability. They also showed hepatic 16s rRNA presence and elevated conjugated bile acids (BAs), particularly taurocholic acid (TCA) and taurodeoxycholic acid (TDCA), in portal serum. These BAs promoted hepatocyte injury and activated liver macrophages, enhancing inflammation both in vitro and in vivo. Fecal microbiome analysis revealed reduced abundance of bile salt hydrolase (BSH)-expressing bacteria. Fecal microbiota transplantation from Spp1[ΔIEC] mice or treatment with a BSH inhibitor further worsened MASH.

CONCLUSION: IEC-derived OPN protects against MASH by modulating BA composition and shaping the gut microbiome.},
}

@article {pmid41241177,
year = {2025},
author = {Rinaldi, M and Gatti, M and Giannella, M},
title = {Avoiding resistance development to newer drugs: open research lines.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2025.11.009},
pmid = {41241177},
issn = {1469-0691},
abstract = {BACKGROUND: The spread of multidrug-resistant Gram-negative bacteria (MDR-GNB), particularly those with carbapenem-resistant (CR) or difficult-to-treat resistance (DTR) phenotypes, is a major public health threat. New agents offer potent therapeutic options but carry the challenge of preserving their effectiveness against resistance.

OBJECTIVE: This narrative review summarizes antimicrobial and non-antimicrobial strategies to prevent or mitigate resistance development to novel agents.

SOURCES: We searched PubMed-MEDLINE for English-language articles published in the last five years.

CONTENT: Among antimicrobial strategies, we reviewed the role of optimizing pharmacokinetic/pharmacodynamic (PK/PD) targets for novel beta-lactam/beta-lactamase inhibitor combinations (BL/BLIc) and the impact of combination versus monotherapy regimens. Achieving aggressive joint PK/PD targets may help prevent resistance, supported by approaches such as continuous infusion of time-dependent agents and therapeutic drug monitoring. Current evidence does not demonstrate a routine benefit of combination therapy over monotherapy for novel drugs; however, available studies are limited in size and quality, and resistance emergence has rarely been a primary endpoint. Non-antimicrobial strategies reviewed include fecal microbiota transplantation (FMT), phage therapy, and active or passive immunization. These approaches may reduce the burden of MDR-GNB, particularly in high-risk populations such as immunocompromised patients, those undergoing invasive procedures, or patients with foreign bodies. By lowering pathogen load and transmission, these interventions could enhance the effectiveness of current drugs and limit further resistance development.

IMPLICATIONS: Prevention of resistance to novel BL/BLIc currently relies on optimized dosing and infusion strategies. The benefit of combination regimens remains uncertain and warrants further investigation, ideally with resistance emergence as a defined endpoint and addressed with appropriate analysis. Non-antimicrobial interventions show promise as adjunctive tools in high-risk settings and merit integration into broader resistance prevention frameworks.},
}

@article {pmid41240539,
year = {2025},
author = {Ma, J and Li, Y and Yang, Y and Zhao, L and Jiang, Y and Wong, TW and Zhang, D},
title = {Gut-liver axis mechanisms of Hippophae rhamnoides L. in non-alcoholic fatty liver disease prevention.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157517},
doi = {10.1016/j.phymed.2025.157517},
pmid = {41240539},
issn = {1618-095X},
abstract = {BACKGROUND: Phytosterol-rich Hippophae rhamnoides L. can ameliorate abnormal blood lipids in patients with non-alcoholic fatty liver disease (NAFLD). Its gut microbiota modulatory roles along gut-liver axis are not known.

OBJECTIVE: This study explored the preventive roles of H. rhamnoides L. against NAFLD and the associated gut-liver axis mechanisms.

METHODS: Sterols were extracted from H. rhamnoides L. seed oil (SHR) and subjected to LC-MS analysis. Their effects on body/liver/epididymal fat mass, intestinal microbiota, metabolites (DAO, D-LA, LPS) and SCFAs secretion, intestinal barrier (claudin-1, ZO-1) and liver lipid composition and molecular biology (AST, ALT, TC, TG, LDL-C, HDL-C, SREBP1c, SCD1, FAS, LXRα, PPARα) were examined in vivo against normal and high-fat diet mice. The modulatory action of microbiota on liver dysfunction was further verified through SHR-fed fecal transplantation into antibiotic-pretreated mice.

RESULTS: β-sitosterol, campesterol, stigmasterol, and ergosterol were the primary active constituents of SHR. With reference to high fat diet mice, SHR increased intestinal tight junction functionality, reducing inflammatory LPS migration to liver and hepatic lipid synthesis. SHR raised the relative abundance of Alloprevotella and Lachnospiraceae_NK4A136_group, and Bacteroides/Firmicutes ratio leading to increased SCFA secretion that strengthened intestinal barrier and reduced hepatic hyperlipidemia.

CONCLUSION: SHR effectively mitigated NAFLD by reducing hepatic lipid expression via regulating intestinal microbiota, its SCFA secretion and intestinal barrier.},
}

@article {pmid41239983,
year = {2025},
author = {Gabriel-Segard, T and Heberden, C and Mondot, S and Duquesnoy, M and Dicembre, M and Naudon, L and Philippe, C and Maximin, E and Blais, A and Jacota, M and Lapaque, N and Blottière, HM and Paul, S and Doré, J and Rabot, S and Hanachi, M},
title = {Anorexia nervosa symptoms are induced after specific gut microbiota dysbiosis transfer in germ-free mice.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2563701},
doi = {10.1080/19490976.2025.2563701},
pmid = {41239983},
issn = {1949-0984},
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Anorexia Nervosa/microbiology/therapy/physiopathology ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; Mice ; Mice, Inbred BALB C ; Female ; Disease Models, Animal ; Humans ; Germ-Free Life ; Feces/microbiology ; Adult ; Male ; },
abstract = {Anorexia nervosa (AN) is the most severe and life-threatening eating disorder. Its pathophysiology remains largely unknown, and no effective treatment currently exists for severe forms of the disease. Gut microbiota (GM) dysbiosis has been consistently reported in AN; however, no study has yet considered the role of the microbiota within the full spectrum of AN symptoms. To investigate the direct involvement of the microbiota in disease symptoms, we developed a murine model of fecal microbiota transplantation (FMT), using germ-free BALB/c mice colonized with fecal samples from well-characterized AN patients and healthy controls. Physiological, organ, and behavioral parameters were systematically monitored. We found that key AN-related features (including food restriction, anxiety-like behavior, physical hyperactivity, and elevated inflammatory responses) were transmitted to germ-free mice following transplantation with AN-derived microbiota. Likewise, organ-specific alterations associated with AN, such as liver dysfunction and disruption of ovarian follicles, were also reproduced. In conclusion, we demonstrate that the transfer of AN microbiota induces behavioral, physiological, and organ-level alterations reminiscent of the human disease. These findings highlight a major role of the gut microbiota in the symptomatology and progression of AN and open new therapeutic perspectives targeting this ecosystem.},
}

Animals
*Gastrointestinal Microbiome/physiology
*Anorexia Nervosa/microbiology/therapy/physiopathology
*Dysbiosis/microbiology
*Fecal Microbiota Transplantation
Mice
Mice, Inbred BALB C
Female
Disease Models, Animal
Humans
Germ-Free Life
Feces/microbiology
Adult
Male

@article {pmid41239968,
year = {2025},
author = {Kim, MS and Bisanz, JE},
title = {Design and application of synthetic human gut microbial communities.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2575923},
doi = {10.1080/19490976.2025.2575923},
pmid = {41239968},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation/methods ; Dysbiosis/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Host Microbial Interactions ; Bacteria/genetics/classification ; Animals ; },
abstract = {The gut microbiome shapes host health through a complex network driven by both host‒microbe and microbe‒microbe interactions. Disruption of these interactions, often referred to as dysbiosis, is associated with a range of infectious and chronic diseases. Owing to the success of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridioides difficile infection, FMT has been explored as a therapeutic option for a range of microbiota-associated conditions, including inflammatory bowel disease and obesity. However, the microbial diversity that is the greatest strength of FMT is also its greatest liability. Concerns relating to reliance on human donors, potential for transmission of multidrug-resistant organisms or undesirable phenotypes demonstrate a need for alternate approaches, including the generation of synthetic alternatives to FMT, which can be built in the laboratory from individual strains. Furthermore, these communities are powerful tools for conducting mechanistic research allowing for the generation of 'knockout' communities, which are not possible when working with undefined fecal transplants. This review examines strategies for designing synthetic microbial communities that represent a new generation of microbiome-derived therapies. We highlight how synthetic microbial communities are being used to answer mechanistic questions about host-microbiome interactions relevant to health and disease. Finally, we examine the current clinical translation of these communities as live biotherapeutic products (LBPs). While the regulatory frameworks for LBPs continue to evolve, early clinical successes illuminate the potential for synthetic microbial communities to treat complex human diseases through targeted manipulation and restoration of the gut microbiome.},
}

Humans
*Gastrointestinal Microbiome
Fecal Microbiota Transplantation/methods
Dysbiosis/therapy/microbiology
Inflammatory Bowel Diseases/therapy/microbiology
Host Microbial Interactions
Bacteria/genetics/classification
Animals

@article {pmid41238277,
year = {2025},
author = {Pai, N and Sainath, NN},
title = {Diagnosis and Management of Small Intestinal Bacterial Overgrowth in Pediatric Short Bowel Syndrome.},
journal = {Gastroenterology clinics of North America},
volume = {54},
number = {4},
pages = {805-821},
doi = {10.1016/j.gtc.2025.07.005},
pmid = {41238277},
issn = {1558-1942},
mesh = {Humans ; *Short Bowel Syndrome/microbiology/complications/therapy ; *Intestine, Small/microbiology ; Child ; Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Microbiome ; Breath Tests ; *Blind Loop Syndrome/diagnosis/therapy ; },
abstract = {This article explores the diagnosis and management of small intestinal bacterial overgrowth in children with short bowel syndrome, a population affected by altered anatomy, dysmotility, and medication-related risk factors. Diagnostic accuracy is limited by the feasibility, and specificity of breath testing and small bowel aspirates. While antibiotics are commonly used, concerns about recurrence and antibiotic resistance remain significant. Emerging nutritional strategies and precision-based, microbiome-targeted therapies offer promising adjunctive treatment options.},
}

Humans
*Short Bowel Syndrome/microbiology/complications/therapy
*Intestine, Small/microbiology
Child
Anti-Bacterial Agents/therapeutic use
Gastrointestinal Microbiome
Breath Tests
*Blind Loop Syndrome/diagnosis/therapy

@article {pmid41238092,
year = {2025},
author = {Ye, M and Ju, H and Ren, G and Hu, J},
title = {The Role of Microbiome in Immunotherapy: Insights and Perspectives.},
journal = {Seminars in cancer biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.semcancer.2025.11.001},
pmid = {41238092},
issn = {1096-3650},
abstract = {The intricate interplay between the gut microbiome and the host immune system has been recognized as a pivotal determinant of clinical outcomes in cancer immunotherapy. Mounting evidence suggests that specific microbial communities are associated with both the efficacy and toxicity of immune checkpoint inhibitors in diverse malignancies, underscoring the microbiome's role in modulating systemic and tumour-localized immunity. Mechanistically, the microbiome shapes antitumour immunity by affecting antigen presentation, activation of effector cells, immunosuppression and adverse effects. Key microbial components and metabolites present in distinct anatomical niches have been identified as promoters or inhibitors of therapeutic responsiveness via multiple pathways. Harnessing this knowledge, microbiome-targeted strategies such as antibiotic, probiotic, fecal microbiota transplantation, and dietary modulation are regarded as potential adjuvant therapies to enhance the efficacy of anti-tumour therapies. Although significant progress has been achieved in preclinical studies, challenges persist in translating these findings into standardized clinical applications.},
}

@article {pmid41237834,
year = {2025},
author = {Yang, J and Li, J},
title = {Nanotechnology-Microbiota Synergy in Cancer Immunotherapy.},
journal = {Critical reviews in oncology/hematology},
volume = {},
number = {},
pages = {105018},
doi = {10.1016/j.critrevonc.2025.105018},
pmid = {41237834},
issn = {1879-0461},
abstract = {The global burden of cancer continues to escalate, yet the efficacy of current targeted therapies and immune checkpoint inhibitors (ICIs) is often hampered by drug resistance and immune escape. The gut microbiota orchestrates tumor progression and ICI efficacy bidirectionally via the "microbiota-immune-tumor" axis. However, traditional interventions, including fecal microbiota transplantation and antibiotics, are limited by inherent drawbacks such as poor targeting. Nanotechnology can overcome this limitation: it not only enables precise targeting of the gut microbiota and reshapes the tumor immune microenvironment to synergistically enhance ICI efficacy but also reverses drug resistance in tumor chemotherapy, radiotherapy, and targeted therapy through multiple strategies. Additionally, it can synergize with probiotics, extracellular vesicles, and other agents to achieve tumor therapy. This review synthesizes current understanding of gut microbiota-immune crosstalk, the microbiota's role in regulating ICI efficacy, and the central applications of nanotechnology, thereby proposing novel synergistic strategies for cancer treatment.},
}

@article {pmid41237775,
year = {2025},
author = {Van Hul, M and Cani, PD},
title = {From microbiome to metabolism: Bridging a two-decade translational gap.},
journal = {Cell metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmet.2025.10.011},
pmid = {41237775},
issn = {1932-7420},
abstract = {The mapping of the human genome sparked high expectations for biomedical breakthroughs, yet attention has since shifted toward the human microbiome as a key player in health and disease. Pioneering studies revealed striking inter-individual variability and numerous associations between gut microbiota and a wide range of conditions (i.e., obesity, diabetes, cardiovascular and inflammatory bowel diseases, autism, allergies, neurodegenerative diseases, and cancers). However, the field has faced a deluge of correlative "dysbiosis" studies with limited causal evidence. Although animal models have provided crucial mechanistic insights, translating these findings to humans has proven challenging. Interventions such as fecal microbiota transplantation, prebiotics, probiotics, and postbiotics often yield inconsistent or modest effects in clinical trials. This gap highlights the need for precision, functional profiling, and integration of multi-omics , for instance, through artificial intelligence. In this perspective, we discuss what microbiome research offers as a transformative shift and how we conceptualize disease, favoring systems biology and personalized interventions over reductionist approaches.},
}

@article {pmid41236646,
year = {2025},
author = {Ochi, T and Takeda, M and Asahara, T and Kurita, A and Ogata, Y and Suzuki, M and Takei, H and Nittono, H and Miyano, G and Koga, H and Lane, GJ and Okazaki, T and Saiura, A and Mizuta, K and Kasahara, M and Yamataka, A and Yamashiro, Y},
title = {Postoperative gut dysbiosis in biliary atresia patients treated by portoenterostomy or liver transplantation.},
journal = {Pediatric surgery international},
volume = {42},
number = {1},
pages = {9},
pmid = {41236646},
issn = {1437-9813},
support = {22K11861//Japan Society for the Promotion of Science KAKENHI grant/ ; },
mesh = {Humans ; *Biliary Atresia/surgery ; *Dysbiosis/microbiology/etiology ; *Liver Transplantation/adverse effects ; Male ; Female ; *Portoenterostomy, Hepatic/adverse effects ; *Gastrointestinal Microbiome ; *Postoperative Complications/microbiology ; Infant ; Feces/microbiology/chemistry ; Bile Acids and Salts/analysis ; Case-Control Studies ; },
abstract = {PURPOSE: To assess how surgery and management protocols affect gut microbiota in postoperative biliary atresia (BA) patients by comparing survivors with native livers (NL) or transplanted livers (TL) with healthy non-surgical controls (CL).

METHODS: Subjects were 62 post-portoenterostomy BA patients divided into 2 groups (NL and TL) and CL. All subjects were clinically stable with no dietary restrictions throughout the study period. Stool samples were compared for gut microbiota, organic acids, and fecal bile acids, while blood samples were compared for serum biochemistry and serum bile acids.

RESULTS: Stool samples from CL (n = 30) were normal while NL (n = 31) and TL (n = 31) showed gut dysbiosis with significantly decreased total bacteria and reduced predominance of obligate anaerobes, and an abundance of Clostridioides difficile, Enterobacteriaceae, and Enterococcus. The latter two were more abundant in TL than NL. Biochemistry was normal in TL. In NL, elevated AST/ALT correlated with increased Clostridioides difficile, decreased Bacteroides fragilis group, and decreased Lactobacilli. Fecal secondary bile acids were lower and serum primary and secondary bile acids were higher in NL and TL compared with CL.

CONCLUSION: Gut dysbiosis was present in both NL and TL. Pathogenic florae were more abundant in TL despite TL biochemistry being normal.},
}

Humans
*Biliary Atresia/surgery
*Dysbiosis/microbiology/etiology
*Liver Transplantation/adverse effects
Male
Female
*Portoenterostomy, Hepatic/adverse effects
*Gastrointestinal Microbiome
*Postoperative Complications/microbiology
Infant
Feces/microbiology/chemistry
Bile Acids and Salts/analysis
Case-Control Studies

@article {pmid41235136,
year = {2025},
author = {Wu, Y and Pan, S and Yin, C and Kong, Y and Huo, W and Wang, Q and Wu, J and Li, L and Wei, J and Lu, C and Han, L and Lu, Y},
title = {PSORI-CM02 Restores Epidermal Differentiation in Psoriasis via the Gut Microbiota-Sphingolipid Axis.},
journal = {Drug design, development and therapy},
volume = {19},
number = {},
pages = {9993-10010},
pmid = {41235136},
issn = {1177-8881},
mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Psoriasis/drug therapy/metabolism/pathology ; Mice ; Humans ; *Cell Differentiation/drug effects ; *Sphingolipids/metabolism ; *Epidermis/drug effects/pathology/metabolism ; Keratinocytes/drug effects/metabolism ; },
abstract = {BACKGROUND: Psoriasis is linked to gut dysbiosis and disturbed sphingolipid metabolism. PSORI-CM02 improves epidermal differentiation, yet its impact on the microbiota-sphingolipid axis remains unknown.

METHODS: Transcriptomics of patient keratinocytes, Carmofur inhibition in IMQ mice, and multi-omics (metabolomics, metagenomics) of skin, lymph nodes and gut were combined. SPF, PGF and GF mice underwent FMT to test microbiota dependency.

RESULTS: Psoriatic lesions showed sphingolipid pathway enrichment. Carmofur enhanced differentiation. PSORI-CM02 lowered PASI, spleen index, and tissue levels of ceramide, S1P, C1P and sphingomyelin while restoring Flg, Krt10 and Krt14. It reduced Turicibacter, Bacteroides, Bifidobacterium and Acetobacter. PSORI-CM02-derived microbiota reproduced therapeutic effects in all FMT settings.

CONCLUSION: PSORI-CM02 reshapes gut microbiota, normalizes sphingolipid metabolism and improves epidermal differentiation to treat psoriasis.},
}

*Gastrointestinal Microbiome/drug effects
Animals
*Psoriasis/drug therapy/metabolism/pathology
Mice
Humans
*Cell Differentiation/drug effects
*Sphingolipids/metabolism
*Epidermis/drug effects/pathology/metabolism
Keratinocytes/drug effects/metabolism

@article {pmid41234596,
year = {2025},
author = {Du, Y and Li, Y and Yu, M and Yu, Y and Zhang, Y and Wang, X and He, J and Lin, L and Shen, B and Gong, Y and Zhu, J and Zou, B and Liu, Y and Huang, M and Lu, Y},
title = {Fecal microbiota transplantation plus immune checkpoint inhibitor rechallenges in patients with advanced non-small cell lung cancer: a single-arm exploratory study.},
journal = {Translational lung cancer research},
volume = {14},
number = {10},
pages = {4541-4559},
pmid = {41234596},
issn = {2218-6751},
abstract = {BACKGROUND: The management of advanced non-small cell lung cancer (NSCLC) after progression on initial immunotherapy represents a significant clinical challenge. Immune checkpoint inhibitor (ICI) rechallenge is a considered option, yet its efficacy remains limited. Strategies to enhance the efficacy of ICI rechallenge are urgently needed. There is a pressing need for novel strategies to sensitize tumors to ICI rechallenge. Previous studies have established a correlation between the gut microbiota and the tumor response to immunotherapy, and have explored the application of fecal microbiota transplantation (FMT) in modifying the immune response by restoring the gut microbiota. However, the potential of FMT from healthy donor to reverse immunotherapy resistance in patients with NSCLC has not been previously investigated. This preliminary study aimed to provide initial insights into the safety, tolerability, and potential efficacy of the combined therapy of FMT from healthy donor with immunotherapy rechallenge in NSCLC patients.

METHODS: In this single-arm exploratory study, patients with advanced NSCLC who progressed after prior immunotherapy were screened and enrolled based on predefined eligibility criteria, including prior response to ICIs and adequate organ function. Eligible patients received oral FMT capsules from healthy donors followed by rechallenge with camrelizumab. The primary endpoint was safety and feasibility [incidence of adverse events (AEs) graded by CTCAE v5.0]. Secondary end points included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Fecal and blood samples were collected for exploratory analyses of microbiota, metabolome, and T cell receptor (TCR) repertoire.

RESULTS: Seven patients (all male, median age 55 years) were enrolled and constituted the analysis population. The majority (5/7) had received three or more prior lines of therapy. During the follow-up period, none experienced grade 4 or higher AEs. The treatment-related AEs were mainly associated with immunotherapy, and only grade 1 FMT-related AEs (e.g., nausea, diarrhea, bloating, and constipation) were reported. One patient achieved a partial response (PR) and one achieved stable disease (SD) with PFS times of 14.6 and 8.1 months, respectively. The median PFS was 1.5 months [95% confidence interval (CI): 1.24-1.75], and the OS was 12.1 months (95% CI: 0.3-23.9) for all patients. Moreover, the treatment modulated the composition of the intestinal flora in all patients, with alpha diversity increasing in responders and decreasing in non-responders.

CONCLUSIONS: The results indicated that the combined therapy of FMT and immunotherapy rechallenge was feasible and demonstrated a tolerable safety profile in this small cohort. The observed clinical activity is preliminary. These findings support the need for larger, controlled trials to assess the efficacy of this approach.},
}

@article {pmid41234231,
year = {2025},
author = {Huang, L and Wang, S and Zhang, H and Feng, S and Zhong, H and Chen, J and Xie, W and Wu, L and Zhang, T and He, X and Yang, J},
title = {Clinical efficacy evaluation of washed microbiota transplantation treatment for metabolic related fatty liver disease and its impact on tongue coating microorganisms.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1684173},
pmid = {41234231},
issn = {1664-2392},
mesh = {Humans ; Animals ; *Tongue/microbiology ; Mice ; Male ; Female ; Middle Aged ; *Microbiota ; *Fecal Microbiota Transplantation/methods ; Adult ; Mice, Inbred C57BL ; Treatment Outcome ; RNA, Ribosomal, 16S/genetics ; *Non-alcoholic Fatty Liver Disease/therapy/microbiology ; },
abstract = {OBJECTIVE: The present study aims to explore the impact of washed microbiota transplantation (WMT) on the tongue microbiota composition of individuals with metabolic-associated fatty liver disease (MAFLD) and elucidate its biological correlations.

METHODS: We conducted a comprehensive analysis of hepatic fat deposition and characterized the tongue coating microbiota using 16S rRNA gene sequencing in MAFLD patients before and after undergoing WMT treatment. Furthermore, a MAFLD mouse model was established for additional validation.

RESULTS: At the genus level, significant differences in tongue coating microbiota structure were observed between MAFLD patients and HC. Specifically, Neisseria positively correlated with the BARD score, Porphyromonas and Rhodococcus positively correlated with fat decay, and Petostreptococcus, a conditionally pathogenic bacterium, exhibited a significantly higher relative abundance in MAFLD patients compared to HC. Conversely, Actinomyces positively correlated with the FIB-4 score, Megasphaera negatively correlated with the APRI score, and Subdoligulum negatively correlated with low-density lipoprotein levels. Notably, following effective WMT treatment, patients exhibited improved symptoms, with a significant reduction in the relative abundance of Petostreptococcus and an increase in potential probiotics such as Lachnospiraceae and Bifidobacterium in their tongue coating microbiota. Additionally, structural differences in the tongue coating microbiota were identified at the genus level between MAFLD model mice and HC mice. After WMT treatment, the relative abundance of conditionally pathogenic bacteria like Enterococcus was significantly decreased in MAFLD model mice.

CONCLUSIONS: WMT not only significantly ameliorates liver fat deposition in MAFLD patients but also alters the tongue coating microbial structure associated with disease severity, thereby potentially mitigating adverse patient outcomes.},
}

Humans
Animals
*Tongue/microbiology
Mice
Male
Female
Middle Aged
*Microbiota
*Fecal Microbiota Transplantation/methods
Adult
Mice, Inbred C57BL
Treatment Outcome
RNA, Ribosomal, 16S/genetics
*Non-alcoholic Fatty Liver Disease/therapy/microbiology

@article {pmid41232540,
year = {2025},
author = {Wieringa, JW and Binyamin, D and Jankelowitz, IA and Schweitzer, R and Turjeman, S and Khatib, S and Esser, MJ and van der Woude, CJ and Fuhler, GM and Koren, O},
title = {Intestinal barrier alterations in mice following fecal microbiota transplant from children of IBD-affected mothers.},
journal = {Med (New York, N.Y.)},
volume = {},
number = {},
pages = {100915},
doi = {10.1016/j.medj.2025.100915},
pmid = {41232540},
issn = {2666-6340},
abstract = {BACKGROUND: Inflammatory bowel disease (IBD) carries a hereditary risk, which is higher through maternal, rather than paternal, inheritance. Like their mothers, children born to mothers with IBD have an altered microbiome shortly after birth.

METHODS: To investigate whether this altered microbiome persists later in life and affects the intestinal mucosa, the fecal microbiome was analyzed in samples from 44 infants ranging from 0 to 10 years of age born to 26 women with IBD. Forty-four age-matched children of 29 women without IBD served as controls. Fecal microbiota transplantation (FMT) to germ-free mice was carried out from 4-year-olds born to mothers with IBD and controls. Markers of inflammation, barrier function, and metabolic changes were investigated.

FINDINGS: Intestinal microbiomes were more similar between women with IBD and their children than between control mothers and their offspring. Microbial changes were noticeable in children from mothers with IBD from the age of 4 years compared to children of controls. No inflammatory response was present in the mucosa of mice receiving FMT from children of mothers with IBD; however, mesenteric lymph node enlargement and decreased expression of barrier genes Zo1 and Ocln were seen in mice receiving FMT from these children compared to controls. Additionally, reduced colonic expression of the immunological tolerance enzyme Ido1 coincided with decreased serum kynurenine/tryptophan ratios.

CONCLUSIONS: Fecal microbiomes of children of mothers with IBD exhibit characteristics that reduce epithelial tight junction barrier genes and tolerogenic tryptophan metabolism. Microbiome-induced gut barrier disruptions may contribute to an enhanced IBD predisposition in infants of mothers with IBD.

FUNDING: This work was funded by ZonMw.},
}

@article {pmid41161092,
year = {2025},
author = {Gu, M and Peng, X and Dai, X and Ma, X and Ge, W and Yang, S and Wei, W},
title = {Tannic acid decreased the synthesis and secretion of sIgA in the small intestine of Brandt's voles (Lasiopodomys brandtii) by modifying gut microbiota.},
journal = {Biochemical and biophysical research communications},
volume = {789},
number = {},
pages = {152846},
doi = {10.1016/j.bbrc.2025.152846},
pmid = {41161092},
issn = {1090-2104},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Arvicolinae/microbiology/immunology ; *Intestine, Small/drug effects/microbiology/metabolism/immunology ; *Tannins/pharmacology ; *Immunoglobulin A, Secretory/metabolism/biosynthesis ; Male ; Fecal Microbiota Transplantation ; Polyphenols ; },
abstract = {Tannic acid (TA), a representative plant secondary metabolite, impairs intestinal immune function and alters intestinal microbiota abundance of Brandt's voles. Whether TA reduces intestinal immune function by modifying the gut microbiota remains unknown. In this study, Brandt's voles were divided into three groups for microbiota transplantation (FMT): normal saline (Ab), microbiota from normal saline administration (R-Con), and microbiota from TA administration (R-TA). Then, the intestinal morphology, immune indices, gut flora, and microbiota metabolites were measured after FMT. The findings showed that the sIgA content of small intestine of voles in the R-TA group were lower than in the R-con group. Additionally, the voles in the R-con group exhibited higher mRNA levels of PIgR, J-chain, BAFF, and APRIL than in the R-TA group. The ANOSIM results showed significant structural differentiation, reflecting that the β-diversity of the cecal microbiome was altered. Moreover, the voles in the R-con group had a higher concentration of butyric acid in the cecum compared to both the Ab and R-TA groups. In the experiment 2, the sIgA content in the duodenum and ileum of Brandt's voles in the TBA group (1200 mg•kg[-1]d[-1] TA + butyrate) was significantly higher than that in the TNS group (1200 mg•kg[-1]d[-1] TA + normal saline). To summarize, the "TA microbiota" decreased the slgA secretion and synthesis in the small intestine by reducing butyric acid content, thus lowering the intestinal immune capacity of Brandt's voles. The findings provide the experimental basis to prove the critical role of gut microorganisms in controlling animal physiological processes.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Arvicolinae/microbiology/immunology
*Intestine, Small/drug effects/microbiology/metabolism/immunology
*Tannins/pharmacology
*Immunoglobulin A, Secretory/metabolism/biosynthesis
Male
Fecal Microbiota Transplantation
Polyphenols

@article {pmid41232361,
year = {2025},
author = {Bishoyi, AK and Al-Hasnaawei, S and Salem, KH and Ganesan, S and Shankhyan, A and Nanda, A and Sinha, A and Ray, S and Nathiya, D and Hammady, FJ},
title = {Gut microbiome metabolites in lung cancer: The emerging importance of short-chain fatty acids.},
journal = {International immunopharmacology},
volume = {168},
number = {Pt 1},
pages = {115821},
doi = {10.1016/j.intimp.2025.115821},
pmid = {41232361},
issn = {1878-1705},
abstract = {Short-chain fatty acids (SCFAs), which are produced from the fermentation by the gut microbiota of dietary fiber, are now proven to play a vital role in the growth control of lung cancer and drug response. SCFAs have mechanisms of action, including the inhibition of histone deacetylases, activation of G-protein-coupled receptors, and metabolic reprogramming. SCFAs suppress tumor growth, induce apoptosis, suppress angiogenesis, and modulate epithelial-mesenchymal transition. Besides the above direct antitumor effects, SCFAs enhance the therapeutic effect of immune checkpoint inhibitors and reduce the toxicity of radiotherapy and chemotherapy by maintaining the mucosal barrier and restoring systemic immune homeostasis. Butyrate function is highly dualistic; it is usually protective but may confer multidrug resistance under certain therapeuticconditions. To reconcile these opposing effects is akey challenge in the translation of microbiota-based therapeutics and interventions. Therapies such as probiotics, fecal microbiota transplantation, and designed microbial consortia all target SCFAs as central mediators of microbiome-host communication. Overall, SCFAs are candidate metabolic co-adjuvants that can maximize therapeutic efficacy, suppress unacceptable side effects, and redirect therapeutic approaches to lung cancer.},
}

@article {pmid41229982,
year = {2025},
author = {Chen, Z and Li, L and Jin, D and Zhao, Y and Malard, F and Huang, H and Ye, Y and Mohty, M},
title = {Gut microbiota and acute graft-versus-host disease.},
journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu},
volume = {37},
number = {5},
pages = {657-666},
pmid = {41229982},
issn = {1000-9604},
abstract = {Acute graft-versus-host disease (aGVHD) is an important complication which critically impacts the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation. Increasing evidence suggests that dysbiosis of the gut microbiota plays a key role in aGVHD pathogenesis. The biological process involves compromised intestinal barrier integrity, amplified inflammation driven by the translocation of microbial products like lipopolysaccharide, and finally the dysregulated immune response centralized by T cell activation and differentiation. Meanwhile, certain microbial metabolites such as short-chain fatty acids and secondary bile acids exert protective effects. The clinical relevance of these findings is underscored by studies establishing that specific gut microbial signatures, such as low diversity and single pathogen dominance, independently predict aGVHD morbidity and mortality. From a therapeutic perspective, the microbiome has emerged as an important therapeutic target for aGVHD. Fecal microbiota transplantation has shown significant efficacy in clinical trials for prophylaxis and treatment of aGVHD, providing definitive proof-of-concept for ecological restoration. This review synthesizes these foundational mechanistic insights, from metabolic disruption to host-microbe crosstalk at the mucosal barrier, and details the rapidly advancing clinical landscape of microbiome-targeted diagnostics and therapeutics for aGVHD.},
}

@article {pmid41229686,
year = {2025},
author = {Tian, R and Chong, CJ and Bai, YY and Chen, N and Qiao, RR and Wang, K and Wang, YW and Zhao, P and Zhao, CB and Tang, YP and Zhang, L and Zhang, Q},
title = {The role of gut microbiota in diarrhea and its alleviation through microbiota-targeted interventions.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1630823},
pmid = {41229686},
issn = {1664-302X},
abstract = {Diarrhea is a common gastrointestinal disease and closely related to the balance of the gut microbiota (GM). In turn, dysregulation of the GM can affect the onset and progression of diarrhea through regulating the metabolism, intestinal immune function, intestinal barrier function and changes in the brain-gut axis of host. Although increasing evidence suggests that GM is associated with gastrointestinal homeostasis and disease, the underlying mechanisms are not fully understood. GM disorder was often accompanied by diarrhea patients and animals, and the diarrhea caused by GM imbalance mainly involved the effects on short chain fatty acids (SCFAs), bile acids (BAs), intestinal barrier, immune system, and brain-gut microbiota axis (BGMA). In addition, intervening in the GM (probiotics, fecal microbiota transplantation and bacteriophage therapy) has been shown to be an effective way to alleviate diarrhea. In this review, the mechanism of diarrhea occurrence, probiotics, fecal microbiota transplantation and bacteriophage therapy intervene in diarrhea by regulating GM from basic and clinical research were summarized and discussed. We aim to provide the latest reference for studying the mechanism of treating diarrhea from the perspective of GM, and provide data support for clinical treatment of diarrhea.},
}

@article {pmid41229548,
year = {2025},
author = {Xiao, Y and Wei, L and Yu, J and Liu, Y},
title = {Fecal Microbiota Transplantation for Attention-Deficit/Hyperactivity Disorder: Mechanisms, Evidence, and Future Directions.},
journal = {International journal of general medicine},
volume = {18},
number = {},
pages = {6757-6767},
pmid = {41229548},
issn = {1178-7074},
abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. While pharmacological and behavioral therapies remain first-line treatments, their limitations in efficacy, tolerability, and long-term adherence underscore the need for innovative interventions. Growing evidence highlights the role of the microbiota-gut-brain axis (MGBA) in ADHD pathophysiology, particularly involving immune dysregulation, neurotransmitter imbalance, metabolic disruption, and epigenetic alterations. Fecal microbiota transplantation (FMT), as a microbiota-based intervention, has shown promise in restoring MGBA homeostasis and modulating neural function through multiple mechanisms. This review summarizes current preclinical and clinical research on FMT in ADHD, covering its effects on neuroinflammation, neurotransmitter pathways, vagus nerve and HPA axis signaling, and epigenetic reprogramming. Although preclinical models and early human data indicate potential behavioral benefits and mechanistic plausibility, methodological heterogeneity, limited sample sizes, and incomplete mechanistic validation pose significant challenges. Future research should prioritize protocol standardization, randomized controlled trials, biomarker discovery, and ethical regulation to facilitate the safe and effective clinical translation of FMT in ADHD treatment.},
}

@article {pmid41228422,
year = {2025},
author = {Diotaiuti, P and Misiti, F and Marotta, G and Falese, L and Calabrò, GE and Mancone, S},
title = {The Gut Microbiome and Its Impact on Mood and Decision-Making: A Mechanistic and Therapeutic Review.},
journal = {Nutrients},
volume = {17},
number = {21},
pages = {},
doi = {10.3390/nu17213350},
pmid = {41228422},
issn = {2072-6643},
support = {MUR Decree n. 105123.06.2022 PNRR Missione 4 Componente 2 Investimento 1.5-CUP H33C22000420001//Project ECS0000024 "Ecosistema dell'innovazione-Rome Technopole" financed by EU NextGeneration EU plan/ ; },
mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Affect/physiology ; *Decision Making/physiology ; Animals ; Cognition ; Probiotics ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; },
abstract = {Background/Objectives: The gut microbiome is increasingly recognized as a key modulator of central nervous system function through the gut-brain axis. Dysbiosis has been associated with neuropsychiatric disorders such as depression, anxiety, impulsivity, cognitive decline, and addiction. This review aims to synthesize mechanistic insights and therapeutic perspectives on how gut microbiota influence mood regulation, decision-making, and cognitive processes. Methods: A comprehensive narrative review was conducted using peer-reviewed articles retrieved from PubMed, Scopus, and Web of Science up to August 2025. Studies were included if they explored microbiota-related effects on behavior, mood, cognition, or decision-making using human or animal models. Emphasis was placed on molecular mechanisms, microbiome-targeted therapies, and multi-omics approaches. Results: Evidence indicates that gut microbiota modulate neurochemical pathways involving serotonin, dopamine, GABA, and glutamate, as well as immune and endocrine axes. Microbial imbalance contributes to low-grade systemic inflammation, impaired neuroplasticity, and altered stress responses, all of which are linked to mood and cognitive disturbances. Specific microbial taxa, dietary patterns, and interventions such as probiotics, prebiotics, psychobiotics, and fecal microbiota transplantation (FMT) have shown promise in modulating these outcomes. The review highlights methodological advances including germ-free models, metagenomic profiling, and neuroimaging studies that clarify causal pathways. Conclusions: Gut microbiota play a foundational role in shaping emotional and cognitive functions through complex neuroimmune and neuroendocrine mechanisms. Microbiome-based interventions represent a promising frontier in neuropsychiatric care, although further translational research is needed to define optimal therapeutic strategies and address individual variability.},
}

*Gastrointestinal Microbiome/physiology
Humans
*Affect/physiology
*Decision Making/physiology
Animals
Cognition
Probiotics
Dysbiosis/microbiology
Fecal Microbiota Transplantation
Prebiotics/administration & dosage

@article {pmid41226824,
year = {2025},
author = {de Groen, P and Blok, LCHM and Fuhri Snethlage, CM and Hanssen, NMJ and Rampanelli, E and Nieuwdorp, M},
title = {Unraveling Type 1 Diabetes: Integrating Microbiome, Metabolomics, and Immunomodulation for Next-Generation Therapies.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
doi = {10.3390/ijms262110788},
pmid = {41226824},
issn = {1422-0067},
support = {09150182010020//Personal NWO-VICI grant 2020/ ; 101141346//ERC Advanced grant/ ; 4-SRA-2025-1766-M-B//BREAKTHROUGH T1D Grant/ ; 09150172210050//ZonMw-VIDI grant 2023/ ; 2021T055//Senior Clinical Dekker grant by the Dutch Heart Foundation/ ; 09150172210019//ZONMW-VIDI grant 2023/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 1/therapy/immunology/metabolism/microbiology ; *Gastrointestinal Microbiome/immunology ; *Metabolomics/methods ; *Immunomodulation ; Animals ; Fecal Microbiota Transplantation ; Autoimmunity ; },
abstract = {Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T-cell-mediated destruction of pancreatic beta cells, resulting in insulin deficiency. Both genetic predisposition and environmental factors contribute to T1D development, with growing evidence implicating the gut microbiome as a critical environmental modulator in disease pathogenesis. Gut microbial composition and derived metabolites influence immune homeostasis and autoimmunity. This review summarizes recent advances elucidating immune dysregulations in T1D and novel therapeutic strategies to preserve beta cell function. We discuss approaches such as immune cell engineering, including CAR-Treg therapy, and targeted modulation of immune signaling pathways like JAK-STAT. Furthermore, we explore the role of the gut microbiota and its metabolites in modulating host immunity and describe emerging microbiome-targeting interventions, including fecal microbiota transplantation and metabolite supplementation. These interventions show promise in modulating disease progression in preclinical and early clinical studies. An integrated understanding of immune and microbiome-related mechanisms is critical for developing next-generation therapies. Further research and clinical trials are needed to optimize these approaches and translate them into durable, personalized treatments for individuals with T1D.},
}

Humans
*Diabetes Mellitus, Type 1/therapy/immunology/metabolism/microbiology
*Gastrointestinal Microbiome/immunology
*Metabolomics/methods
*Immunomodulation
Animals
Fecal Microbiota Transplantation
Autoimmunity

@article {pmid41223655,
year = {2025},
author = {Chen, J and Gu, M and Zhang, M and Wang, S and Zhang, X and Zhu, Z and Gan, Q},
title = {Stage-specific gut microbial restructuring drives estrous transition in rabbits.},
journal = {Animal bioscience},
volume = {},
number = {},
pages = {},
doi = {10.5713/ab.250529},
pmid = {41223655},
issn = {2765-0189},
abstract = {OBJECTIVE: This study aimed to investigate the relationship between colonic microbiota and estrous cycle transition in rabbits by integrating 16S rRNA gene sequencing and metabolomic analyses, and to identify key microbial taxa and metabolites involved in estrus regulation.

METHODS: Female New Zealand white rabbits were divided into diestrus and early estrus groups based on vulvar mucosa color and serum estradiol (E2) concentration. Colonic microbiota dynamics were assessed via 16S rRNA sequencing, while metabolomes of colonic contents were profiled using UHPLC-MS/MS. Fecal microbiota transplantation (FMT) was performed by orally administration of colonic contents from diestrus or early estrus rabbits to mice with disrupted estrous cycles, to evaluate the regulatory effects of microbiota. Exogenous indole-3-acetic acid (IAA) was administered to both mice and rabbits to assess its role in estrus onset and cyclicity restoration.

RESULTS: Colonic microbial composition differed significantly between diestrus and early estrus rabbits. The genera Anaerostipes and Ruminiclostridium were enriched in early estrus, while the genera Oscillospirales UCG_010 and UCG_005 were more abundant in diestrus. FMT from early estrus donors restored cyclicity in mice with disrupted cycles, whereas diestrus FMT did not. Metabolomics identified IAA as a key elevated metabolite in early estrus, and this metabolite accelerated estrus onset and restored cyclicity in both mice and rabbits.

CONCLUSION: These findings demonstrate that gut microbiota restructuring regulates the estrous transition of rabbits, providing a basis for developing microbiota-targeted strategies to enhance reproductive efficiency in rabbit production and optimize animal reproductive management.},
}

@article {pmid40751372,
year = {2025},
author = {Bryant, JA and Straub, TJ and Pardi, DS and Litcofsky, KD and Kelly, CR and Chafee, ME and Cohen, SH and Khanna, S and Berenson, CS and Wortman, J and Sims, M and Ford, CB and Lombardo, MJ and McGovern, BH and von Moltke, L and Kraft, CS and Henn, MR and Hasson, BR},
title = {Comparability of Gastrointestinal Microbiome and Bile Acid Profiles in Patients With First or Multiply Recurrent Clostridioides difficile Infection.},
journal = {The Journal of infectious diseases},
volume = {232},
number = {5},
pages = {e733-e740},
doi = {10.1093/infdis/jiaf408},
pmid = {40751372},
issn = {1537-6613},
support = {//Seres Therapeutics/ ; },
mesh = {Humans ; *Bile Acids and Salts/analysis/metabolism ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology/drug therapy/therapy ; Male ; Female ; Feces/microbiology/chemistry ; Middle Aged ; *Clostridioides difficile ; Aged ; Recurrence ; Anti-Bacterial Agents/therapeutic use ; Adult ; Fecal Microbiota Transplantation ; },
abstract = {BACKGROUND: Clostridioides difficile infection (CDI) treatment guidelines suggest varied approaches for patients with first (frCDI) or multiply recurrent CDI (mrCDI). Low microbial diversity, elevated primary bile acids (BA), and low secondary BA concentrations favor germination of C. difficile spores into toxin-producing bacteria and are believed to increase rCDI risk. Greater understanding of the gastrointestinal (GI) microbiome in rCDI may inform management of the disease. We describe a post hoc comparison of GI microbiome and bile acid profiles between patients with frCDI and mrCDI in a Phase 3 open-label trial, ECOSPOR IV, of fecal microbiota spores, live-brpk (VOWST®; VOS, formerly SER-109), an orally-administered live microbiome therapeutic.

METHODS: Patients received VOS following symptom resolution after standard-of-care antibiotics. Pretreatment baseline (within 3 days following antibiotic completion) and Week 1 post-dosing stool samples were collected for whole metagenomic sequencing and metabolomics. Diversity was calculated from MetaPhlAn2 species profiles. Concentrations of primary and secondary BAs were measured via targeted LC-MS/MS.

RESULTS: rCDI rates through Week 8 were similarly low in both frCDI and mrCDI patients (6.5% versus 9.7%, respectively). Baseline microbial diversity was similarly low between frCDI and mrCDI subgroups (P > .05). Diversity and secondary BA concentrations increased in both subgroups, whereas primary BA concentrations declined following VOS dosing, leading to few differences between subgroups at Week 1.

CONCLUSIONS: These data suggest commonalities in microbiome disruption in patients with frCDI and mrCDI that contribute to recurrence and suggest that antibiotics followed by a live microbiome therapy may be an optimal treatment strategy for rCDI, regardless of number of prior CDI recurrences.},
}

Humans
*Bile Acids and Salts/analysis/metabolism
*Gastrointestinal Microbiome
*Clostridium Infections/microbiology/drug therapy/therapy
Male
Female
Feces/microbiology/chemistry
Middle Aged
*Clostridioides difficile
Aged
Recurrence
Anti-Bacterial Agents/therapeutic use
Adult
Fecal Microbiota Transplantation

@article {pmid41223536,
year = {2025},
author = {Toresson, L and Ludvigsson, U and Olmedal, G and Hellgren, J and Toni, M and Giaretta, PR and Suchodolski, JS and Blake, AB},
title = {Repeated fecal microbiota transplantation in dogs with chronic enteropathy can decrease disease activity and corticosteroid usage.},
journal = {Journal of the American Veterinary Medical Association},
volume = {},
number = {},
pages = {1-10},
doi = {10.2460/javma.25.08.0563},
pmid = {41223536},
issn = {1943-569X},
abstract = {OBJECTIVE: Evaluate clinical and fecal parameters in dogs with refractory chronic enteropathy (CE) treated with repeated fecal microbiota transplantation (FMT) as adjunct treatment.

METHODS: This was a prospective longitudinal observational study from September 25, 2021, to June 20, 2024. Thirty-nine dogs received 2 to 3 rectal FMTs over 1 month. Canine inflammatory bowel disease activity index (CIBDAI) and fecal samples were assessed for 6 months. Fecal samples were analyzed for dysbiosis index, bile acids, and calprotectin.

RESULTS: 28 of 39 dogs responded to FMT. Eight dogs had a short-lasting response. Before FMT, baseline CIBDAI was equivalent in responders and nonresponders. Responders had a significantly decreased CIBDAI at 1 month, which remained unaltered at 6 months in long-lasting responders (LLRs). Baseline dysbiosis index (mean [95% CI]) was significantly lower in LLRs (-0.02 [-3.3 to 2.7]) versus nonresponders and short-lasting responders combined (N/SRs; 2.9 [-0.2 to 6.0]). Baseline percentage of secondary unconjugated fecal bile acids was higher in LLRs (65 [41 to 89]) versus N/SRs (30 [6 to 54]). Dysbiosis index decreased significantly at the time point for the third FMT in LLRs (-2.4 [-3.9 to 2.2]) but not in N/SRs (3.3 [-0.4 to 5.7]). Corticosteroid tapering was achieved in 13 responders. Mild adverse events were noted in 4 dogs.

CONCLUSIONS: This repeated FMT protocol was an effective adjunct treatment in refractory CE dogs, especially in dogs with no or mild dysbiosis. Marked dysbiosis and BA dysmetabolism before and after FMT appeared associated with no clinical response or a short-lasting response to FMT, potentially requiring repeated FMT.

CLINICAL RELEVANCE: Repeated FMT could reduce disease activity and corticosteroid usage in dogs with refractory CE.},
}

@article {pmid41220843,
year = {2025},
author = {Kwon, K and Kim, M and Jung, Y and Yoon, MY and Lee, JY and Yoon, SS and Rho, M and Chung, YW and Ryu, JH},
title = {Intestinal Dysbiosis Caused by Epithelial Fabp6 Gene Disruption Exacerbates Gut Inflammatory Disease.},
journal = {Immune network},
volume = {25},
number = {5},
pages = {e35},
pmid = {41220843},
issn = {1598-2629},
abstract = {Ileal lipid binding protein (Ilbp), encoded by Fabp6 gene, plays a critical role in intracellular transport of bile acids (BAs) from apical to basolateral side of ileal enterocytes, maintaining BA homeostasis within enterohepatic circulation. However, pathophysiological consequences of Ilbp deficiency remain largely unexplored. Here, we demonstrate that disruption of BA balance, caused by intestinal epithelial cell (IEC)-specific Fabp6 gene knockout (Fabp6 [ΔIEC]), exacerbates dextran sulfate sodium (DSS)-induced gut inflammation. Fecal microbiota transplantation from Fabp6 [ΔIEC] mice to germ free recipient mice replicated the adverse effects observed in Fabp6 [ΔIEC] mice, which were mitigated when these mice were co-housed with control (Fabp6 [f/f]) mice. Metagenomic analysis identified Ligilactobacillus murinus as a primarily diminished strain in Fabp6 [ΔIEC] mice. Oral administration of L. murinus isolated from feces of Fabp6 [f/f] mice ameliorated DSS-induced colitis in Fabp6 [ΔIEC] mice by restoring epithelial barrier integrity and lowering pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. Furthermore, daily administration of taurodeoxycholic acid-one of the BAs reduced in Fabp6 [ΔIEC] mice and that promotes the growth of L. murinus in an in vitro growth assay-also exhibited a protective effect against DSS-induced colitis through a similar mechanism. These findings suggest that deficiency of specific BAs due to epithelial Fabp6 deletion leads to gut dysbiosis, predisposing the host to inflammatory disease.},
}

@article {pmid41219783,
year = {2025},
author = {Sami, A and Ashraf, R and Nisar, S and Mustehsan, ZH and Javed, MA and Ozsahin, DU and Waheed, Y},
title = {A comprehensive narrative review on precision medicine approach to hypertension: exploring the role of genetics, epigenetics, microbiome, and artificial intelligence.},
journal = {Journal of health, population, and nutrition},
volume = {44},
number = {1},
pages = {394},
pmid = {41219783},
issn = {2072-1315},
abstract = {Hypertension (HTN) impacts approximately 1.28 billion individuals globally and poses a great burden of disease. The objectives of this study are to explore the role of genetics, epigenetics, microbiome, and artificial intelligence (AI) in the management of HTN. A thorough literature search was conducted across various databases including PubMed, Google Scholar, Web of Science (WoS), and Medline to retrieve articles related to the role of genetics, epigenetics, microbiome, and AI in the precision medicine of HTN. Genes-including ACE, NOS3, ADD1, CYP11B2, NPPA, and NPPB-have a profound impact on blood pressure (BP) regulation in our body and polymorphism in these key genes can lead to HTN. Up or down-regulation of genes by epigenetic factors such as miRNA-155, miRNA-210, and miRNA-122 can significantly contribute to the development of HTN. These genetic and epigenetic factors can also be used as specific targets for gene editing and gene therapy for long-term management of HTN. However, the implementation of these techniques has not been possible in clinical settings due to lack of human studies and safety concerns related to unpredictable DNA alterations, nucleotide deletions, and loss of allele-specific chromosomes. Modulation of gut microbiome through oral supplements, fecal microbiota transplant (FMT), and dietary interventions has emerged as one the most effective and safe techniques for managing HTN in human models. AI-based cutting-edge models have helped curate personalized diet plans based on an individual's unique microbiome, genomic information, and physiological conditions leading to a reduction in BMI, fat, BP, and heart rate while improving overall cardiac health and gut microbial diversity. Despite the significant advantages offered by AI-based medicine, ethical concerns-related to data privacy, bias, and discrimination-and ineffective models have led to limited integration of AI in precision medicine of HTN. The integration of genetics, epigenetics, microbiome, and AI-based models can play a key role in improving the current landscape of precision medicine of HTN. These cutting-edge techniques can lead to a shift from the current one-size-fits all approach to more personalized treatment plan however further research in human models is needed to determine the safety and true efficacy of these techniques. Additionally, new AI-models need to be developed that address ethical concerns and are effective in real-world clinical settings.},
}

@article {pmid41219653,
year = {2025},
author = {Lamba, JK and Tandon, C and Tandon, S},
title = {Gut Microbiota and Chronic Kidney Disease: A Complex Interplay with Implications for Diagnosis and Treatment.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {41219653},
issn = {1867-1314},
abstract = {Chronic kidney disease (CKD) progresses over the years with a steady loss of renal function, often culminating in renal failure. While diabetes and hypertension are the major drivers, the exact underlying molecular mechanism for CKD remains only partially understood. Emerging research has revealed a new paradigm, linking microbiota imbalance or dysbiosis with CKD. Dysbiosis leads to the development of uremic toxins, which aggravate kidney damage, inflammation, and metabolic disruptions that accelerate disease progression. This review explores the complex interactions between dysbiosis, uremic toxins, and the major risk factors, namely, diabetes and hypertension. Microbiome-targeted interventions, such as dietary interventions, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), are discussed with an emphasis on their therapeutic relevance in influencing renal health. Additionally, the potential of genetic engineering, particularly CRISPR-based systems, to develop 'smart bacteria' designed to restore gut health is also examined. Future perspectives highlight the need for personalized therapies targeting the gut-kidney axis. Incorporating microbiome modulation into standard CKD treatments holds the potential to slow disease progression, enhance recovery, and improve the quality of life for patients.},
}

@article {pmid41217998,
year = {2025},
author = {Wei, Q and Rui, M and Wang, Y and Ng, SC and You, JHS},
title = {Cost-effectiveness analysis of fecal microbiota transplantation for patients with irritable bowel syndrome.},
journal = {Digestion},
volume = {},
number = {},
pages = {1-21},
doi = {10.1159/000549485},
pmid = {41217998},
issn = {1421-9867},
abstract = {BACKGROUND AND AIM: Studies have demonstrated clinical benefits of fecal microbiota transplantation (FMT) for treatment of irritable bowel syndrome (IBS). This study aimed to evaluate the cost-effectiveness of FMT versus standard drug treatment for patients with moderate-to-severe IBS who failed to respond to first-line therapy from the US payer's perspective.

METHODS: Two one-year Markov models were developed to examine the outcomes of FMT versus standard drug treatment in patients with constipation-predominant IBS (IBS-C) and diarrhea-predominant IBS (IBS-D). The primary model outcomes included direct medical cost and quality-adjusted life-years (QALYs) gained. Model inputs were obtained from literature and public data. Sensitivity analyses were performed to examine the robustness of model results.

RESULTS: In the base-case analysis, FMT gained higher QALYs (by 0.0159 QALYs for IBS-C and 0.0166 QALYs for IBS-D) with cost-savings (USD7,813 for IBS-C and USD8,979 for IBS-D) when compared to standard drug treatment. Key influential parameters identified by one-way sensitivity analysis were response probabilities of FMT and first-line treatment, the utility values of therapeutic response and nonresponse, and FMT cost. The probabilities of FMT to be accepted as the preferred strategy at a willingness-to-pay threshold of 50,000 USD/QALY were 99.91% and 99.89% for IBS-C and IBS-D, respectively.

CONCLUSIONS: FMT appears to be cost-effective for patients with moderate-to-severe IBS who failed to respond to first-line therapy from the US payer's perspective.},
}

@article {pmid41216880,
year = {2025},
author = {Gu, C and Xu, R and Yin, B and Wu, R and Wei, Y and Wang, D and Wei, W},
title = {Sex-Specific Involvement of Gut Microbiota in Behavioral and Endocrine Responses to Chronic Predator Odor in Brandt's Voles.},
journal = {Integrative zoology},
volume = {},
number = {},
pages = {},
doi = {10.1111/1749-4877.13014},
pmid = {41216880},
issn = {1749-4877},
support = {32401290//National Natural Science Foundation of China/ ; 31770422//National Natural Science Foundation of China/ ; //the Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; },
abstract = {Predator cues have profound impacts on the behavior and physiology of prey animals. However, the mechanisms underlying stress responses induced by chronic exposure to predator cues in mammals, particularly the role of the gut microbiota, remain insufficiently understood. This study investigated how gut microbiota contributes to behavioral and physiological responses in Brandt's voles (Lasiopodomys brandtii) under chronic predator odor exposure. Adult voles were repeatedly exposed to cat feces odor (CO) for 18 days (1 h/day), followed by behavioral tests to assess anti-predator and anxiety-like behaviors, hormonal measurements to evaluate basal hypothalamic-pituitary-adrenal (HPA) axis activity, and 16S rRNA sequencing to analyze gut microbiota composition. The results showed that repeated CO exposure increased anxiety-like behaviors and basal HPA axis activity in both sexes. However, anti-predator behaviors exhibited sex-specific responses: Males were habituated to repeated CO exposure by reducing freezing and alerting behaviors, whereas females consistently displayed concealing strategies, reflecting different adaptive strategies to prolonged predator threats. While CO exposure did not alter the α-diversity of gut microbiota, it significantly affected the β-diversity in females, including a reduction in the relative abundance of Treponema and Quinella. Cecal microbiota transplantation from female CO-exposed voles to naive recipients increased anxiety-like behaviors and basal HPA levels but did not alter anti-predator behaviors in the recipients. In contrast, male recipients showed no significant behavioral or physiological changes. These findings suggest that gut microbiota is involved in regulating anxiety-like behavior and HPA axis activity in female voles but has a limited regulating role in male voles.},
}

@article {pmid41214728,
year = {2025},
author = {Tang, X and You, X},
title = {Progress and prospects of gut microbiota-targeted therapy for primary biliary cholangitis.},
journal = {Gut pathogens},
volume = {17},
number = {1},
pages = {86},
pmid = {41214728},
issn = {1757-4749},
abstract = {Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease. Current therapeutic options are limited, with some patients responding poorly to first-line treatment with ursodeoxycholic acid. However, second-line drugs are difficult to develop. There are no drugs available to treat liver dysfunction. Currently, the etiology of PBC is unknown, and the intestinal flora affects the liver through the gut‒liver axis. The hypothesis of intestinal dysbiosis has gradually been accepted and involves mechanisms such as leaky gut, abnormal bile acids metabolism, and dysregulated immune tolerance. We found that gut microbiota-targeted therapy, including antibiotics, dietary regulation, probiotic supplementation, and fecal microbiota transplantation, can effectively improve liver function, remodel the intestinal microbiota, and alleviate symptom. However, this therapy has limitations, such as large individual differences and unknown long-term efficacy and safety. Large-scale and long-term clinical studies are expected to promote the broad application of gut microbiota-targeted therapy in the clinic.},
}

@article {pmid41212912,
year = {2025},
author = {Zhao, C and Ming, S and Zhang, J and Huang, T and Du, Y and Liu, J and Zong, S},
title = {Alleviative Effect of Stropharia rugosoannulata Exopolysaccharide on d-Galactose-Induced Gut Inflammation and Oxidative Stress by Modulating Gut Microbiota.},
journal = {Chemistry & biodiversity},
volume = {},
number = {},
pages = {e02918},
doi = {10.1002/cbdv.202502918},
pmid = {41212912},
issn = {1612-1880},
support = {137012023//Yangzhou University/ ; BY20221437//Joint Project of Industry-University-Research of Jiangsu Province/ ; },
abstract = {The exopolysaccharide SREP-1, purified from the fermentation broth of Stropharia rugosoannulata, exhibited antiaging potential. As aging significantly alters gut structure and function, protective effect of SREP-1 was investigated using a d-galactose-induced aging mouse model. SREP-1 administration reversed D-galactose-induced body weight loss and colon damage, as evidenced by improved histopathology. SREP-1 mitigated weight loss and colon damage, enhanced the activities of antioxidants (SOD, GSH-Px, and CAT), and reduced the level of MDA. It decreased proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and elevated IL-10 in colon tissue, while boosting serum immunoglobulins (IgG and IgM). Crucially, these effects were abolished by antibiotic pretreatment, highlighting the role of gut microbiota in SREP-1 bioactivity. This role was further confirmed through fecal microbiota transplantation (FMT) and fecal supernatant transplantation (FST) experiments. Based on 16S rRNA sequencing, SREP-1 restored gut microbial diversity, increased beneficial genera (e.g., Faecalibacterium, Akkermansia, Lactobacillus, and Bacteroides), and decreased harmful bacteria (e.g., Escherichia-Shigella and Collinsella). Furthermore, short-chain fatty acids (SCFAs) levels were elevated in the SREP-1 group, which might regulate GPCRs/NF-κB/Nrf2 signaling pathways and exert biological activity. This study revealed the potential of SREP-1 to alleviate aging-related intestinal dysfunction and underscored the crucial role of gut microbiota in mediating these effects.},
}

@article {pmid41211636,
year = {2025},
author = {Wu, L and Zhang, Q and Tang, Z and Li, Y and Wu, T and Chen, L and Tan, C and Zhang, L and Ji, X and Zhang, S and Wu, Y and Bozec, A and Zaiss, MM and Luo, Y},
title = {Gut microbiota-derived tryptophan indole metabolites ameliorate collagen-induced arthritis in mice via aryl hydrocarbon receptor activation in T cells and intestinal epithelial cells.},
journal = {Arthritis & rheumatology (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/art.43430},
pmid = {41211636},
issn = {2326-5205},
abstract = {OBJECTIVE: To investigate the specific role of tryptophan metabolism, especially that of microbiome-derived metabolites, in the development of rheumatoid arthritis (RA).

METHODS: We employed metabolomics to profile metabolites in 53 high-risk for RA individuals (PreRAs), 30 established RA patients and 38 healthy individuals. Fecal microbiota transplantation (FMT) and collagen-induced arthritis (CIA) mouse models were used to investigate the impact of gut microbiome on arthritis severity, gut barrier function, and metabolic change. Treg cell differentiation and epithelial cells' barrier function were assessed by flow cytometry, immunofluoresence staining and western blotting. Co-immunoprecipitation and luciferase were applied for molecular mechanism studies.

RESULTS: Dysregulated tryptophan metabolism exists in RA and PreRA individuals, as well as in FMT mice, characterized by a shift toward the kynurenine pathway and reduced activity of serotonin and indole pathways. Indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA) significantly alleviated arthritis in CIA mice by expanding Treg cells via the classical aryl hydrocarbon receptor (AhR)-aryl hydrocarbon receptor nuclear translocator (ARNT)-xenobiotic response element (XRE) signaling pathway. Moreover, ILA repaired the leaking gut by increasing Zo-1 and occludin expression in Caco-2 cells, which was blocked by AhR antagonist CH223191. Moreover, CH223191 treatment could significantly reverse the improving effects of ILA and IAA on arthritis in mice.

CONCLUSION: These findings indicate that Trp indole metabolites may play a negative regulatory role in the progression of RA by affecting Treg cell development and intestinal gut barrier function.},
}