Pub Date : 2026-01-11DOI: 10.1080/19490976.2025.2609457
Maarten van de Guchte,Stanislas Mondot,Julie Cadiou,Ruma Raghuvanshi,Colombe Rous,Joël Doré
Fecal microbiota transfer (FMT) has been used with variable success in the experimental treatment of ulcerative colitis (UC), and efforts to improve its efficacy very much remain a matter of trial and error. We recently predicted that atypical donor microbiota could improve results. Here, we provide experimental support for this prediction in a rat model where we induced a transition of the intestinal ecosystem to an alternative state characterized by chronic low-grade inflammation and dysbiosis. While autologous FMT did barely or not enhance the restoration of a healthy microbiota compared to a control group without FMT, the atypical allogenic microbiota from one of two donor rat strains proved remarkably successful in the restoration of a healthy microbiota, in some cases accompanied by a healthy distal colon histology. These results allow the rationalization of research efforts towards improvement of FMT efficacy in humans, and indicate that (initial) success of FMT should be monitored at the microbiota level as much as at the level of clinical symptoms. More importantly, they provide further support for our earlier published, clinical-data-based, conceptual model of the intestinal ecosystem which suggests promising opportunities for therapeutic innovation in UC treatment. This model notably predicts that, and explains why, symbio-therapy, acting on both microbiota and inflammation, may be more efficient than conventional inflammation-directed therapies, and can be used to guide and monitor treatments.
{"title":"Improving ulcerative colitis prospects through fecal microbiota transfer: atypical donor microbiota can boost success rate.","authors":"Maarten van de Guchte,Stanislas Mondot,Julie Cadiou,Ruma Raghuvanshi,Colombe Rous,Joël Doré","doi":"10.1080/19490976.2025.2609457","DOIUrl":"https://doi.org/10.1080/19490976.2025.2609457","url":null,"abstract":"Fecal microbiota transfer (FMT) has been used with variable success in the experimental treatment of ulcerative colitis (UC), and efforts to improve its efficacy very much remain a matter of trial and error. We recently predicted that atypical donor microbiota could improve results. Here, we provide experimental support for this prediction in a rat model where we induced a transition of the intestinal ecosystem to an alternative state characterized by chronic low-grade inflammation and dysbiosis. While autologous FMT did barely or not enhance the restoration of a healthy microbiota compared to a control group without FMT, the atypical allogenic microbiota from one of two donor rat strains proved remarkably successful in the restoration of a healthy microbiota, in some cases accompanied by a healthy distal colon histology. These results allow the rationalization of research efforts towards improvement of FMT efficacy in humans, and indicate that (initial) success of FMT should be monitored at the microbiota level as much as at the level of clinical symptoms. More importantly, they provide further support for our earlier published, clinical-data-based, conceptual model of the intestinal ecosystem which suggests promising opportunities for therapeutic innovation in UC treatment. This model notably predicts that, and explains why, symbio-therapy, acting on both microbiota and inflammation, may be more efficient than conventional inflammation-directed therapies, and can be used to guide and monitor treatments.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"93 1","pages":"2609457"},"PeriodicalIF":12.2,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-11DOI: 10.1080/19490976.2025.2611617
Tony W H Tang,Kiramat Ullah,Jia-Jung Lee,Hung-Chih Chen,Patrick C H Hsieh
Gut microbiota research has rapidly expanded our understanding of host-microbe interactions in cardiovascular diseases, yet translation of these insights remains challenged by species-specific differences and substantial population heterogeneity. In this review, we synthesize current evidence across rodents, swine, non-human primates, and multi-ethnic human cohorts to delineate conserved versus context-dependent features of the gut-heart axis. Rodent models remain indispensable for mechanistic discovery, enabling causal testing through germ-free, antibiotic-treated, and humanized microbiota platforms, whereas large-animal models better replicate human cardiac anatomy, physiology, and microbial ecology. Human studies provide essential clinical relevance, demonstrating that patients with myocardial infarction, coronary artery disease, atrial fibrillation, and heart failure harbor distinct microbial and metabolite signatures. However, these findings vary across populations due to differences in diet, lifestyle, host genetics, medication exposure, and environmental transitions. Despite taxonomic variability, several functional pathways, most notably short-chain fatty acid production, bile acid biotransformation, and aromatic amino acid metabolism generating molecules such as trimethylamine-N-oxide and phenylacetylglutamine, consistently associate with cardiovascular risk. At the same time, population-specific features, including glycan-microbe interactions shaped by ABO and FUT2 genotypes, diet-responsive metabolite profiles, and variable drug-microbiome interactions, highlight the importance of genetic and environmental context. By integrating cross-species and cross-population evidence, this review outlines a framework for identifying robust microbial pathways, clarifying their translational boundaries, and guiding the development of microbiota-informed diagnostics and interventions that account for biological, cultural, and environmental diversity.
肠道菌群研究迅速扩展了我们对心血管疾病中宿主-微生物相互作用的理解，但这些见解的翻译仍然受到物种特异性差异和大量种群异质性的挑战。在这篇综述中，我们综合了啮齿类动物、猪、非人类灵长类动物和多种族人类群体的现有证据，以描绘肠-心轴的保守特征与环境依赖特征。啮齿动物模型对于机制发现仍然是不可或缺的，可以通过无菌、抗生素治疗和人源化的微生物群平台进行因果检验，而大型动物模型可以更好地复制人类心脏解剖、生理和微生物生态。人体研究提供了必要的临床相关性，证明心肌梗死、冠状动脉疾病、心房颤动和心力衰竭患者具有不同的微生物和代谢物特征。然而，由于饮食、生活方式、宿主遗传、药物暴露和环境转变的差异，这些发现在人群中有所不同。尽管分类上存在差异，但一些功能途径，尤其是短链脂肪酸产生、胆酸生物转化和芳香族氨基酸代谢产生的分子，如三甲胺- n -氧化物和苯乙酰谷氨酰胺，始终与心血管风险相关。与此同时，人群特异性特征，包括ABO和FUT2基因型形成的聚糖-微生物相互作用，饮食反应代谢物谱和可变的药物-微生物相互作用，突出了遗传和环境背景的重要性。通过整合跨物种和跨种群的证据，本综述概述了一个框架，用于识别强大的微生物途径，澄清其翻译边界，并指导微生物群诊断和干预措施的发展，以解释生物，文化和环境多样性。
{"title":"Comparative insights into the gut-heart axis: cross-species and cross-population perspectives.","authors":"Tony W H Tang,Kiramat Ullah,Jia-Jung Lee,Hung-Chih Chen,Patrick C H Hsieh","doi":"10.1080/19490976.2025.2611617","DOIUrl":"https://doi.org/10.1080/19490976.2025.2611617","url":null,"abstract":"Gut microbiota research has rapidly expanded our understanding of host-microbe interactions in cardiovascular diseases, yet translation of these insights remains challenged by species-specific differences and substantial population heterogeneity. In this review, we synthesize current evidence across rodents, swine, non-human primates, and multi-ethnic human cohorts to delineate conserved versus context-dependent features of the gut-heart axis. Rodent models remain indispensable for mechanistic discovery, enabling causal testing through germ-free, antibiotic-treated, and humanized microbiota platforms, whereas large-animal models better replicate human cardiac anatomy, physiology, and microbial ecology. Human studies provide essential clinical relevance, demonstrating that patients with myocardial infarction, coronary artery disease, atrial fibrillation, and heart failure harbor distinct microbial and metabolite signatures. However, these findings vary across populations due to differences in diet, lifestyle, host genetics, medication exposure, and environmental transitions. Despite taxonomic variability, several functional pathways, most notably short-chain fatty acid production, bile acid biotransformation, and aromatic amino acid metabolism generating molecules such as trimethylamine-N-oxide and phenylacetylglutamine, consistently associate with cardiovascular risk. At the same time, population-specific features, including glycan-microbe interactions shaped by ABO and FUT2 genotypes, diet-responsive metabolite profiles, and variable drug-microbiome interactions, highlight the importance of genetic and environmental context. By integrating cross-species and cross-population evidence, this review outlines a framework for identifying robust microbial pathways, clarifying their translational boundaries, and guiding the development of microbiota-informed diagnostics and interventions that account for biological, cultural, and environmental diversity.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"39 1","pages":"2611617"},"PeriodicalIF":12.2,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-11DOI: 10.1080/19490976.2026.2612804
Maeva Duquesnoy,Benoit Chassaing
The colonic mucus layer is a dynamic barrier that plays central roles in intestinal health, and recent studies highlight that it harbors a distinct and functionally critical microbial community. However, most in vitro gut models fail to recapitulate this mucosal niche, limiting mechanistic investigation of microbiota-mucus interactions. Here, we developed the MBRA 3.0 system, a next-generation chemostat engineered to integrate mucus-coated carriers and enable high-throughput dissection of spatial microbiome dynamics. Using fecal microbiota from eight human donors, we report that mucus addition does not impact total bacterial density but selectively shapes microbial community structure, metabolic output, and pro-inflammatory potential in a donor-dependent manner. Notably, MBRA 3.0 resolves stable, compositionally distinct mucus-associated and luminal communities, mirroring in vivo spatial heterogeneity. Integration of this mucosal niche also modulates short-chain fatty acid (SCFA) profiles and inflammatory signatures, highlighting the relevance of the spatial context for intestinal microbiota research. Hence, MBRA 3.0 offers a scalable and customizable platform to model mucus-microbiota interactions, advancing our understanding of gut ecology and supporting translational discovery in gastrointestinal health and disease.
{"title":"MBRA 3.0: integrating the mucus environment for advanced high-throughput in vitro intestinal microbiome modeling.","authors":"Maeva Duquesnoy,Benoit Chassaing","doi":"10.1080/19490976.2026.2612804","DOIUrl":"https://doi.org/10.1080/19490976.2026.2612804","url":null,"abstract":"The colonic mucus layer is a dynamic barrier that plays central roles in intestinal health, and recent studies highlight that it harbors a distinct and functionally critical microbial community. However, most in vitro gut models fail to recapitulate this mucosal niche, limiting mechanistic investigation of microbiota-mucus interactions. Here, we developed the MBRA 3.0 system, a next-generation chemostat engineered to integrate mucus-coated carriers and enable high-throughput dissection of spatial microbiome dynamics. Using fecal microbiota from eight human donors, we report that mucus addition does not impact total bacterial density but selectively shapes microbial community structure, metabolic output, and pro-inflammatory potential in a donor-dependent manner. Notably, MBRA 3.0 resolves stable, compositionally distinct mucus-associated and luminal communities, mirroring in vivo spatial heterogeneity. Integration of this mucosal niche also modulates short-chain fatty acid (SCFA) profiles and inflammatory signatures, highlighting the relevance of the spatial context for intestinal microbiota research. Hence, MBRA 3.0 offers a scalable and customizable platform to model mucus-microbiota interactions, advancing our understanding of gut ecology and supporting translational discovery in gastrointestinal health and disease.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"45 1","pages":"2612804"},"PeriodicalIF":12.2,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-11DOI: 10.1080/19490976.2026.2614115
Yan Li,Yihong Liu,Xubiao Wei,Changfa Wang,Muhammad Zahoor Khan,Qingshan Ma
Probiotic-derived extracellular vesicles (PEVs) are functional nanovesicles secreted by various microbiota. As a novel class of microbial signals, they encapsulate proteins, nucleic acids, lipids, and microbial-associated molecular patterns, emerging as potent modulators of communication between gut microbiota and host immune cells, such as macrophages. Macrophages, as a crucial component of the innate immune system, rely heavily on specific metabolic reprogramming to execute their immune functions effectively. Recent evidence demonstrates the pivotal role of macrophage immunometabolism in orchestrating inflammatory responses and regulating systemic metabolic health. This review provides the first comprehensive synthesis of current evidence linking PEVs to the function and metabolic reprogramming of macrophages. We first conducted a detailed exploration of the release rationale, biosynthesis, composition, uptake by macrophages, and biological activity of PEVs. Subsequently, we elucidated how these vesicles and their cargo influence macrophage polarization through several metabolic pathways, including glycolysis, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and amino acid metabolism. We further explore the implications of macrophage immunometabolism in chronic inflammation and metabolic disorders, including inflammatory bowel disease (IBD), neurodegenerative diseases, and atherosclerosis. Additionally, emerging evidence indicates that PEVs may be influenced by various factors, which in turn can affect host immunity and metabolism. Finally, we briefly discuss the limitations and future challenges in this field. This review highlights new research targets concerning the impact of gut microbiota on host immunity and metabolism.
{"title":"Probiotic extracellular vesicles reprogram macrophage immunometabolism: From gut crosstalk to host health.","authors":"Yan Li,Yihong Liu,Xubiao Wei,Changfa Wang,Muhammad Zahoor Khan,Qingshan Ma","doi":"10.1080/19490976.2026.2614115","DOIUrl":"https://doi.org/10.1080/19490976.2026.2614115","url":null,"abstract":"Probiotic-derived extracellular vesicles (PEVs) are functional nanovesicles secreted by various microbiota. As a novel class of microbial signals, they encapsulate proteins, nucleic acids, lipids, and microbial-associated molecular patterns, emerging as potent modulators of communication between gut microbiota and host immune cells, such as macrophages. Macrophages, as a crucial component of the innate immune system, rely heavily on specific metabolic reprogramming to execute their immune functions effectively. Recent evidence demonstrates the pivotal role of macrophage immunometabolism in orchestrating inflammatory responses and regulating systemic metabolic health. This review provides the first comprehensive synthesis of current evidence linking PEVs to the function and metabolic reprogramming of macrophages. We first conducted a detailed exploration of the release rationale, biosynthesis, composition, uptake by macrophages, and biological activity of PEVs. Subsequently, we elucidated how these vesicles and their cargo influence macrophage polarization through several metabolic pathways, including glycolysis, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and amino acid metabolism. We further explore the implications of macrophage immunometabolism in chronic inflammation and metabolic disorders, including inflammatory bowel disease (IBD), neurodegenerative diseases, and atherosclerosis. Additionally, emerging evidence indicates that PEVs may be influenced by various factors, which in turn can affect host immunity and metabolism. Finally, we briefly discuss the limitations and future challenges in this field. This review highlights new research targets concerning the impact of gut microbiota on host immunity and metabolism.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"48 1","pages":"2614115"},"PeriodicalIF":12.2,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enteric infections remain a leading global cause of morbidity, mortality and economic loss, increasingly compounded by the rise of antimicrobial resistance. The gut microbiome - spanning bacteria, archaea, fungi, protists and viruses - is now recognized as an important mediator that shapes susceptibility to infection, pathogen expansion and disease severity through mechanisms such as colonization resistance, resource competition and immune modulation. Conversely, the gut microbial community can facilitate enteric infection through other processes such as cross-feeding and horizontal gene transfer. In this review, we synthesize correlative and mechanistic evidence currently available on microbiome-pathogen interactions; outline host, environmental and socioeconomic modifiers that affect disease risk across the life course; and evaluate current clinical applications. We highlight key limitations in the field and identify priority areas for future research to refine causal models of microbiome-pathogen ecology and enable targeted diagnostics and therapeutics for preventing and managing enteric infections.
{"title":"The human gut microbiome in enteric infections: from association to translation.","authors":"Qi Yin,Samriddhi Gupta,Efrat Muller,Alexandre Almeida","doi":"10.1080/19490976.2026.2612836","DOIUrl":"https://doi.org/10.1080/19490976.2026.2612836","url":null,"abstract":"Enteric infections remain a leading global cause of morbidity, mortality and economic loss, increasingly compounded by the rise of antimicrobial resistance. The gut microbiome - spanning bacteria, archaea, fungi, protists and viruses - is now recognized as an important mediator that shapes susceptibility to infection, pathogen expansion and disease severity through mechanisms such as colonization resistance, resource competition and immune modulation. Conversely, the gut microbial community can facilitate enteric infection through other processes such as cross-feeding and horizontal gene transfer. In this review, we synthesize correlative and mechanistic evidence currently available on microbiome-pathogen interactions; outline host, environmental and socioeconomic modifiers that affect disease risk across the life course; and evaluate current clinical applications. We highlight key limitations in the field and identify priority areas for future research to refine causal models of microbiome-pathogen ecology and enable targeted diagnostics and therapeutics for preventing and managing enteric infections.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"255 1","pages":"2612836"},"PeriodicalIF":12.2,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1080/19490976.2025.2612582
Heenam Stanley Kim
{"title":"Do Akkermansia mutants underlie to the global metabolic disease epidemic?","authors":"Heenam Stanley Kim","doi":"10.1080/19490976.2025.2612582","DOIUrl":"https://doi.org/10.1080/19490976.2025.2612582","url":null,"abstract":"","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"47 1","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1080/19490976.2025.2611546
Xinyang Chen,Qiqiong Li,Wanyu Zhang,Yushan Xu,Xinke Nie,Xindong Wang,Chunhua Chen,Junhua Xie,Shaoping Nie
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with systemic manifestations, including cognitive impairment linked to gut‒brain axis dysregulation. While probiotic therapies show promise, their mechanisms in mitigating neuropsychiatric comorbidities remain unclear. Here, we investigated the therapeutic potential of Akkermansia muciniphila-derived extracellular vesicles (AmEVs) in a murine model of dextran sulfate sodium (DSS)-induced colitis and associated cognitive deficits. AmEVs administration significantly alleviated colitis severity, as evidenced by improved weight retention, reduced disease activity index scores, and colon length restoration. Concurrently, AmEVs reversed colitis-driven cognitive impairments, restoring Y-maze and novel object recognition performance to baseline levels. Mechanistically, AmEVs repaired intestinal and blood‒brain barrier integrity by upregulating tight junction proteins, suppressed neuroinflammation via reduced hippocampal pro-inflammatory cytokines, and inhibited microglial/astrocyte activation. Gut microbiota analysis revealed that AmEVs-mediated enrichment of beneficial Bifidobacterium and suppression of pathogenic Bacteroides and Mucispirillum, alongside restored short-chain fatty acid (SCFA) production. Crucially, AmEVs bidirectionally regulated tryptophan metabolism, reducing colonic serotonin (5-HT) overproduction while restoring hippocampal 5-HT levels and 5-HT1A receptor expression. This was accompanied by enhanced synaptic plasticity and BDNF upregulation in the hippocampus. Proteomic and biodistribution studies confirmed AmEVs' delivery of metabolic regulators to hippocampal neurons, including the key protein Amuc_1100,directly enhancing 5-HT production in vitro. Our findings establish AmEVs as a multifaceted therapeutic agent that concurrently resolves gut inflammation and cognitive deficits via gut-brain axis modulation, offering novel strategies for IBD-related neuropsychiatric comorbidities. Further research is warranted to validate critical vesicular components and optimize clinical translation.
{"title":"Akkermansia muciniphila-derived extracellular vesicles alleviate colitis-related cognitive impairment via tryptophan metabolic reprogramming of the gut‒brain axis.","authors":"Xinyang Chen,Qiqiong Li,Wanyu Zhang,Yushan Xu,Xinke Nie,Xindong Wang,Chunhua Chen,Junhua Xie,Shaoping Nie","doi":"10.1080/19490976.2025.2611546","DOIUrl":"https://doi.org/10.1080/19490976.2025.2611546","url":null,"abstract":"Ulcerative colitis (UC) is a chronic inflammatory bowel disease with systemic manifestations, including cognitive impairment linked to gut‒brain axis dysregulation. While probiotic therapies show promise, their mechanisms in mitigating neuropsychiatric comorbidities remain unclear. Here, we investigated the therapeutic potential of Akkermansia muciniphila-derived extracellular vesicles (AmEVs) in a murine model of dextran sulfate sodium (DSS)-induced colitis and associated cognitive deficits. AmEVs administration significantly alleviated colitis severity, as evidenced by improved weight retention, reduced disease activity index scores, and colon length restoration. Concurrently, AmEVs reversed colitis-driven cognitive impairments, restoring Y-maze and novel object recognition performance to baseline levels. Mechanistically, AmEVs repaired intestinal and blood‒brain barrier integrity by upregulating tight junction proteins, suppressed neuroinflammation via reduced hippocampal pro-inflammatory cytokines, and inhibited microglial/astrocyte activation. Gut microbiota analysis revealed that AmEVs-mediated enrichment of beneficial Bifidobacterium and suppression of pathogenic Bacteroides and Mucispirillum, alongside restored short-chain fatty acid (SCFA) production. Crucially, AmEVs bidirectionally regulated tryptophan metabolism, reducing colonic serotonin (5-HT) overproduction while restoring hippocampal 5-HT levels and 5-HT1A receptor expression. This was accompanied by enhanced synaptic plasticity and BDNF upregulation in the hippocampus. Proteomic and biodistribution studies confirmed AmEVs' delivery of metabolic regulators to hippocampal neurons, including the key protein Amuc_1100,directly enhancing 5-HT production in vitro. Our findings establish AmEVs as a multifaceted therapeutic agent that concurrently resolves gut inflammation and cognitive deficits via gut-brain axis modulation, offering novel strategies for IBD-related neuropsychiatric comorbidities. Further research is warranted to validate critical vesicular components and optimize clinical translation.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"22 1","pages":"2611546"},"PeriodicalIF":12.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1080/19490976.2025.2611543
Marwan E Majzoub,Fernando S Santiago,Shreeya S Raich,Prakruti Sirigeri,Isidora Simovic,Nicodemus Tedla,Nadeem O Kaakoush
Sutterella wadsworthensis is an enigmatic member of the microbiota, previously reported to be present in healthy humans yet also associated with certain gut diseases and their therapeutic outcomes. Here, we report on S. wadsworthensis classified to S. wadsworthensis_A that encodes an immunoglobulin A (IgA) protease that digests human IgA1 and IgA2 but not mouse IgA. The activity of this IgA protease could influence the trajectory of Campylobacter jejuni infection in human epithelial cells and phagocytosis in primary neutrophils. Comparative genomics and screening of metagenomic samples revealed that the protease shared sequence identity with an IgA protease from a bacterium that colonized other mammals and that S. wadsworthensis harboring IgA protease can be detected in individuals globally. Individuals positive for S. wadsworthensis IgA protease in China and Fiji (detection at >90% similarity) were found to have a different microbiome when compared to individuals where the protease was not detected. Phylogenetic analysis of pathogen IgA proteases along with IgA proteases from members of the microbiota suggested that there may be a unique subset of microbiota-derived IgA proteases. Our results highlight the importance of taxonomic resolution in microbiome studies and identify a subgroup of S. wadsworthensis that may be of potential clinical relevance.
{"title":"Immunoglobulin A protease from Sutterella wadsworthensis modifies outcome of infection with Campylobacter jejuni and is associated with microbiome diversity.","authors":"Marwan E Majzoub,Fernando S Santiago,Shreeya S Raich,Prakruti Sirigeri,Isidora Simovic,Nicodemus Tedla,Nadeem O Kaakoush","doi":"10.1080/19490976.2025.2611543","DOIUrl":"https://doi.org/10.1080/19490976.2025.2611543","url":null,"abstract":"Sutterella wadsworthensis is an enigmatic member of the microbiota, previously reported to be present in healthy humans yet also associated with certain gut diseases and their therapeutic outcomes. Here, we report on S. wadsworthensis classified to S. wadsworthensis_A that encodes an immunoglobulin A (IgA) protease that digests human IgA1 and IgA2 but not mouse IgA. The activity of this IgA protease could influence the trajectory of Campylobacter jejuni infection in human epithelial cells and phagocytosis in primary neutrophils. Comparative genomics and screening of metagenomic samples revealed that the protease shared sequence identity with an IgA protease from a bacterium that colonized other mammals and that S. wadsworthensis harboring IgA protease can be detected in individuals globally. Individuals positive for S. wadsworthensis IgA protease in China and Fiji (detection at >90% similarity) were found to have a different microbiome when compared to individuals where the protease was not detected. Phylogenetic analysis of pathogen IgA proteases along with IgA proteases from members of the microbiota suggested that there may be a unique subset of microbiota-derived IgA proteases. Our results highlight the importance of taxonomic resolution in microbiome studies and identify a subgroup of S. wadsworthensis that may be of potential clinical relevance.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"27 1","pages":"2611543"},"PeriodicalIF":12.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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