Gut Microbes最新文献

{"title":"Impact of peripheral circadian misalignment and alcohol on the resiliency of intestinal barrier and microbiota.","authors":"Laura Tran, Maliha Shaikh, Phillip A Engen, Ankur Naqib, Dulce M Frausto, Vivian Ramirez, Malia Gasteier, Zlata Bogin, Kristi Lawrence, Lijuan Zhang, Shiwen Song, Stefan J Green, Faraz Bishehsari, Christopher B Forsyth, Ali Keshavarzian, Garth R Swanson","doi":"10.1080/19490976.2025.2509281","DOIUrl":"10.1080/19490976.2025.2509281","url":null,"abstract":"<p><p>Circadian organization is involved in many gastrointestinal tract (GIT) functions such as the maintenance of intestinal barrier integrity. There is compelling evidence that perturbation of the circadian clock decreases intestinal epithelial cells' resiliency to alcohol-induced injury. One of the most common causes of circadian misalignment is wrong-time eating (largest meal at dinner) in modern societies. Yet, few studies have examined the importance of peripheral circadian rhythms of the GIT to alcohol consumption. Eating patterns during physiologic rest time, defined as wrong-time eating (WTE), misalign the peripheral circadian clock of the GIT and the body's central clock. This study aims to fill this knowledge gap by testing the hypothesis that: (1) WTE worsens alcohol-induced disruption of intestinal barrier integrity and (2) decreased intestinal barrier resiliency to alcohol effects by WTE-disrupted circadian is, at least in part, due to microbiota dysbiosis. Alcohol (20% v/v) and a restricted timed-food paradigm were administered to PERIOD2 luciferase (PER2:LUC) reporter BL/6 mice for 10 weeks. Intestinal barrier integrity, intestinal (stool) microbiota, and microbial metabolites (cecal-derived) were examined. Peripheral circadian misalignment exacerbated alcohol-induced disruption of intestinal barrier integrity (tight junctional proteins) leading to increased intestinal permeability (<i>p</i> < 0.05). In addition, alcohol consumption changed the intestinal microbiota community, decreasing beneficial short-chain fatty acid-producing taxa. Further, we recapitulated the in vivo phenotype in a colonic organoid model and demonstrated that microbial metabolites from circadian-disrupted, alcohol-fed mice mediate decreased resiliency of intestinal epithelial barrier function. Peripheral circadian misalignment through food timing decreases the resiliency of the intestinal barrier to alcohol-induced injury and this effect is mediated through dysbiotic microbiota metabolites.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2509281"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/19490976.2025.2471120","DOIUrl":"10.1080/19490976.2025.2471120","url":null,"abstract":"","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2471120"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation.","authors":"Jelle Slager, Hanna L Simpson, Ranko Gacesa, Lianmin Chen, Ineke L Tan, Jody Gelderloos, Astrid Maatman, Cisca Wijmenga, Alexandra Zhernakova, Jingyuan Fu, Rinse K Weersma, Gieneke Gonera, Iris H Jonkers, Sebo Withoff","doi":"10.1080/19490976.2025.2489071","DOIUrl":"https://doi.org/10.1080/19490976.2025.2489071","url":null,"abstract":"<p><strong>Background: </strong>Coeliac disease (CeD) is an immune-mediated disorder primarily affecting the small intestine, characterized by an inflammatory immune reaction to dietary gluten. CeD onset results from a multifaceted interplay of genetic and environmental factors. While recent data show that alterations in gut microbiome composition could play an important role, many current studies are constrained by small sample sizes and limited resolution.</p><p><strong>Methods: </strong>To address these limitations, we analyzed fecal gut microbiota from two Dutch cohorts, CeDNN (128 treated CeD patients (tCeD), 106 controls) and the Lifelines Dutch Microbiome Project (24 self-reported tCeD, 654 controls), using shotgun metagenomic sequencing. Self-reported IBS (570 cases, 1710 controls) and IBD (93 cases, 465 controls) were used as comparative conditions of the gastrointestinal tract. Interindividual variation within the case and control groups was calculated at whole microbiome and strain level. Finally, species-specific gene repertoires were analyzed in tCeD patients and controls.</p><p><strong>Results: </strong>Within-individual microbiome diversity was decreased in patients with self-reported IBS and IBD but not in tCeD patients. Each condition displayed a unique microbial pattern and, in addition to confirming previously reported microbiome associations, we identify an increase in the levels of <i>Clostridium sp. CAG:253</i>, <i>Roseburia hominis</i>, and <i>Eggerthella lenta</i>, amongst others. We further show that the observed changes can partially be explained by gluten-free diet adherence. We also observe increased interindividual variation of gut microbiome composition among tCeD patients and a higher bacterial mutation frequency in tCeD that contributes to higher interindividual variation at strain level. In addition, the immotile European subspecies of <i>Eubacterium rectale</i>, which has a distinct carbohydrate metabolism potential, was nearly absent in tCeD patients.</p><p><strong>Conclusion: </strong>Our study sheds light on the complex interplay between the gut microbiome and CeD, revealing increased interindividual variation and strain-level variation in tCeD patients. These findings expand our understanding of the microbiome's role in intestinal health and disease.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2489071"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-restricted feeding promotes glucagon-like peptide-1 secretion and regulates appetite via tryptophan metabolism of gut <i>Lactobacillus</i> in pigs.","authors":"Qiuke Li, Ding Tan, Shijie Xiong, Kaifan Yu, Yong Su, Weiyun Zhu","doi":"10.1080/19490976.2025.2467185","DOIUrl":"10.1080/19490976.2025.2467185","url":null,"abstract":"<p><p>Previous clinical trials have shown that time-restricted feeding can be involved in regulating the metabolic health of humans and animals. However, the underlying mechanism has not been fully explored. In this study, the pig model was employed to simulate four prevalent human eating habits, with the aim of investigating the impact of gut microbiota and microbial metabolites on gut hormone secretion and appetite regulation. Compared to the <i>ad libitum</i> feeding (ALF) pattern, three time-restricted feeding patterns reduced total food intake and eating time. Meanwhile, three time-restricted feeding patterns induced elevated levels of serum and hypothalamic glucagon-like peptide-1 (GLP-1), while suppressing reward-related circuits in the hypothalamus. It is noteworthy that the early time-restricted feeding (eTRF) pattern increased the number of intestinal enteroendocrine cells (EECs) compared to ALF. Metagenomic and metabonomic analyses revealed that three time-restricted feeding patterns induced colonization of <i>Lactobacillus</i> and significantly increased the levels of its metabolite, indole-3-lactic acid (ILA). Dietary supplementation with ILA exhibited an increasing trend in fasting serum GLP-1 level of piglets. <i>In vitro</i> studies with pig intestinal organoids showed the <i>Lactobacillus</i> metabolite ILA enhanced GLP-1 secretion through the promotion of intestinal stem cell differentiation into EECs, rather than activating the ability of EECs to secrete GLP-1. Overall, time-restricted feeding promoted GLP-1 secretion and affected long-term appetite regulation by promoting the colonization of <i>Lactobacillus</i> and modulating microbial tryptophan metabolism.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2467185"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles of <i>Limosilactobacillus fermentum</i> SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism.","authors":"Hyejin Choi, Min-Jin Kwak, Youbin Choi, An Na Kang, Daye Mun, Ju Young Eor, Mi Ri Park, Sangnam Oh, Younghoon Kim","doi":"10.1080/19490976.2025.2474256","DOIUrl":"10.1080/19490976.2025.2474256","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a globally prevalent chronic inflammatory skin disorder. Its pathogenesis remains incompletely understood, resulting in considerable therapeutic challenges. Recent studies have highlighted the significance of the interaction between AD and gut microbiome. In this study, we investigated the effects of probiotic-derived extracellular vesicles on AD. Initially, we isolated and characterized extracellular vesicles from <i>Limosilactobacillus fermentum</i> SLAM 216 (LF216EV) and characterized their composition through multi-omics analysis. Gene ontology (GO) and pathway analysis classified LF216EV proteins into biological processes, molecular functions, and cellular components. Importantly, specific abundance in linoleic, oleic, palmitic, sebacic, and stearic acids indicating upregulated fatty acid metabolism were observed by metabolomic analysis. Furthermore, featured lipid profiling including AcylGlcADG and ceramide were observed in LF216EV. Importantly, in an atopic dermatitis-like cell model induced by TNFα/IFNγ, LF216EV significantly modulated the expression of immune regulatory genes (TSLP, TNFα, IL-6, IL-1β, and MDC), indicating its potential functionality in atopic dermatitis. LF216EV alleviated AD-like phenotypes, such as redness, scaling/dryness, and excoriation, induced by DNCB. Histopathological analysis revealed that LF216EV decreased epidermal thickness and mast cell infiltration in the dermis. Furthermore, LF216EV administration reduced mouse scratching and depression-related behaviors, with a faster onset than the classical treatment with dexamethasone. In the quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we observed a significant increase in the expression levels of <i>htrb2c</i>, <i>sert</i>, and <i>tph-1</i>, genes associated with serotonin, in the skin and gut of the LF216EV-treated group, along with a significant increase in the total serum serotonin levels. Gut microbiome analysis of the LF216EV-treated group revealed an altered gut microbiota profile. Correlation analysis revealed that the genera <i>Limosilactobacillus</i> and <i>Desulfovibrio</i> were associated with differences in the intestinal metabolites, including serotonin. Our findings demonstrate that LF216EV mitigates AD-like symptoms by promoting serotonin synthesis through the modulation of gut microbiota and metabolome composition.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2474256"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial micronutrient sharing, gut redox balance and keystone taxa as a basis for a new perspective to solutions targeting health from the gut.","authors":"Robert E Steinert, Ateequr Rehman, Mehdi Sadaghian Sadabad, Alessio Milanese, Jonas Wittwer-Schegg, Jeremy P Burton, Anneleen Spooren","doi":"10.1080/19490976.2025.2477816","DOIUrl":"10.1080/19490976.2025.2477816","url":null,"abstract":"<p><p>In health, the gut microbiome functions as a stable ecosystem maintaining overall balance and ensuring its own survival against environmental stressors through complex microbial interaction. This balance and protection from stressors is maintained through interactions both within the bacterial ecosystem as well as with its host. As a consequence, the gut microbiome plays a critical role in various physiological processes including maintaining the structure and function of the gut barrier, educating the gut immune system, and modulating the gut motor, digestive/absorptive, as well as neuroendocrine system all of which are crucial for human health and disease pathogenesis. Pre- and probiotics, widely available and clinically established, offer various health benefits primarily by beneficially modulating the gut microbiome. However, their clinical outcomes can vary significantly due to differences in host physiology, diets, individual microbiome compositions, and other environmental factors. This perspective paper highlights emerging scientific insights into the importance of microbial micronutrient sharing, gut redox balance, keystone species, and the gut barrier in maintaining a diverse and functional microbial ecosystem, and their relevance to human health. We propose a novel approach that targets microbial ecosystems and keystone taxa performance by supplying microbial micronutrients in the form of colon-delivered vitamins, and precision prebiotics [e.g. human milk oligosaccharides (HMOs) or synthetic glycans] as components of precisely tailored ingredient combinations to optimize human health. Such a strategy may effectively support and stabilize microbial ecosystems, providing a more robust and consistent approach across various individuals and environmental conditions, thus, overcoming the limitations of current single biotic solutions.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2477816"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIIST305 mitigates gastrointestinal acute radiation syndrome injury and ameliorates radiation-induced gut microbiome dysbiosis.","authors":"Debmalya Mitra, Gabriel K Armijo, Elizabeth H Ober, Shenda M Baker, Helen C Turner, Constantinos G Broustas","doi":"10.1080/19490976.2025.2458189","DOIUrl":"10.1080/19490976.2025.2458189","url":null,"abstract":"<p><p>High-dose radiation exposure results in gastrointestinal (GI) acute radiation syndrome identified by the destruction of mucosal layer, intestinal growth barrier dysfunction, and aberrant inflammatory responses. Further, radiation causes gut microbiome dysbiosis characterized by diminished microbial diversity, mostly commensal bacteria, and the spread of bacterial pathogens that trigger the recruitment of immune cells and the production of pro-inflammatory factors that lead to further GI tissue damage. Currently, there are no U.S. Food and Drug Administration (FDA) approved countermeasures that can treat radiation-induced GI injuries. To meet this critical need, Synedgen Inc. has developed a glycopolymer radiomitigator (MIIST305) that is specifically targeted to the GI tract, which acts by intercalating into the mucus layer and the glycocalyx of intestinal epithelial cells that could potentially ameliorate the deleterious effects of radiation. Male C57BL/6J adult mice were exposed to 13 Gy partial body X-irradiation with 5% bone marrow shielding and MIIST305 was administered on days 1, 3, and 5 post-irradiation. Approximately 85% of the animals survived the irradiation exposure and were apparently healthy until the end of the 30-day study period. In contrast, no control, Vehicle-treated animals survived past day 10 at this radiation dose. We show that MIIST305 improved intestinal epithelial barrier function and suppressed systemic inflammatory responses mediated by radiation-induced pro-inflammatory cytokines. Taxonomic profiling and community structure of the fecal and colonic mucosa microbiota demonstrated that MIIST305 treatment increased microbial diversity and restored abundance of beneficial commensal bacteria, including <i>Lactobacillus</i> and <i>Bifidobacterium</i> genera while suppressing potentially pathogenic bacteria <i>Enterococcus</i> and <i>Staphylococcus</i> compared with Vehicle-treated animals. In summary, MIIST305 is a novel GI-targeted therapeutic that greatly enhances survival in mice exposed to lethal radiation and protects the GI tract from injury by restoring a balanced gut microbiota and reducing pro-inflammatory responses. Further development of this drug as an FDA-approved medical countermeasure is of critical importance.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2458189"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased dietary protein stimulates amino acid catabolism via the gut microbiota and secondary bile acid production.","authors":"Sandra Tobón-Cornejo, Monica Sanchez-Tapia, Rocio Guizar-Heredia, Laura Velázquez Villegas, Lilia G Noriega, Janette Furuzawa-Carballeda, Rogelio Hernández-Pando, Natalia Vázquez-Manjarrez, Omar Granados-Portillo, Adriana López-Barradas, Rosa Rebollar-Vega, Otoniel Maya, Aaron W Miller, Aurora Serralde, Martha Guevara-Cruz, Nimbe Torres, Armando R Tovar","doi":"10.1080/19490976.2025.2465896","DOIUrl":"10.1080/19490976.2025.2465896","url":null,"abstract":"<p><p>Excess amino acids from a protein-rich diet are mainly catabolized in the liver. However, it is still unclear to what extent the gut microbiota may be involved in the mechanisms governing this catabolism. Therefore, the aim of this study was to investigate whether consumption of different dietary protein concentrations induces changes in the taxonomy of the gut microbiota, which may contribute to the regulation of hepatic amino acid catabolism. Consumption of a high-protein diet caused overexpression of HIF-1α in the colon and increase in mitochondrial activity, creating a more anaerobic environment that was associated with changes in the taxonomy of the gut microbiota promoting an increase in the synthesis of secondary bile acids, increased secretion of pancreatic glucagon. This effect was demonstrated in pancreatic islets, where secondary bile acids stimulated the expression of the PC2 enzyme that promotes glucagon formation. The increase in circulating glucagon was associated with an induction of the expression of hepatic amino acid-degrading enzymes, an effect attenuated by antibiotics. Thus, high protein intake in mice and humans induced the increase of different species in the gut microbiota with the capacity to produce secondary bile acids leading to an increase in secondary bile acids and glucagon levels, promoting amino acid catabolism.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2465896"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay of m6A RNA methylation and gut microbiota in modulating gut injury.","authors":"Haixia Wang, Juanjuan Han, Xin-An Zhang","doi":"10.1080/19490976.2025.2467213","DOIUrl":"10.1080/19490976.2025.2467213","url":null,"abstract":"<p><p>The gut microbiota undergoes continuous variations among individuals and across their lifespan, shaped by diverse factors encompassing diet, age, lifestyle choices, medication intake, and disease states. These microbial inhabitants play a pivotal role in orchestrating physiological metabolic pathways through the production of metabolites like bile acids, choline, short-chain fatty acids, and neurotransmitters, thereby establishing a dynamic \"gut-organ axis\" with the host. The intricate interplay between the gut microbiota and the host is indispensable for gut health, and RNA N6-methyladenosine modification, a pivotal epigenetic mark on RNA, emerges as a key player in this process. M6A modification, the most prevalent internal modification of eukaryotic RNA, has garnered significant attention in the realm of RNA epigenetics. Recent findings underscore its potential to influence gut microbiota diversity and intestinal barrier function by modulating host gene expression patterns. Conversely, the gut microbiota, through its impact on the epigenetic landscape of host cells, may indirectly regulate the recruitment and activity of RNA m6A-modifying enzymes. This review endeavors to delve into the biological functions of m6A modification and its consequences on intestinal injury and disease pathogenesis, elucidating the partial possible mechanisms by which the gut microbiota and its metabolites maintain host intestinal health and homeostasis. Furthermore, it also explores the intricate crosstalk between them in intestinal injury, offering a novel perspective that deepens our understanding of the mechanisms underlying intestinal diseases.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2467213"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global stress response regulator <i>oxyS</i> in an adherent-invasive <i>Escherichia coli</i> strain attenuates experimental colitis.","authors":"Diana Arsene, Sandrine Y Tchaptchet, Jonathan J Hansen","doi":"10.1080/19490976.2025.2473518","DOIUrl":"10.1080/19490976.2025.2473518","url":null,"abstract":"<p><p>Crohn's disease and ulcerative colitis in humans and experimental immune-mediated colitis in mice are likely due in part to overactive immune responses to resident intestinal bacteria, including certain strains of adherent-invasive <i>Escherichia coli</i> (<i>E. coli</i>) such as <i>E. coli</i> NC101. We have previously shown that specific <i>E. coli</i> NC101 stress responses are upregulated during experimental colitis and attenuate inflammation. However, the roles of broader stress response pathways in <i>E. coli</i> NC101 during experimental colitis are unknown. We hypothesize that the global stress response regulator in <i>E. coli</i>, <i>oxyS</i>, also reduces experimental colitis. We show that intestinal <i>E. coli</i> NC101 upregulate <i>oxyS</i> expression during colitis in monocolonized interleukin-10 deficient mice. Furthermore, we demonstrate that <i>oxyS</i>-sufficient <i>E. coli</i> NC101 have decreased motility and biofilm formation <i>in vitro</i> and attenuated intestinal translocation and colitogenic potential <i>in</i> <i>vivo</i> compared with <i>oxyS-</i>deficient <i>E. coli</i>. These data suggest that activation of a generalized <i>E. coli</i> stress response, <i>oxyS</i>, reduces experimental colitis and may be a potential therapeutic target.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2473518"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}