Gut Microbes最新文献

{"title":"Systematically-designed mixtures outperform single fibers for gut microbiota support.","authors":"T M Cantu-Jungles, V Agamennone, T J Van den Broek, F H J Schuren, B Hamaker","doi":"10.1080/19490976.2024.2442521","DOIUrl":"https://doi.org/10.1080/19490976.2024.2442521","url":null,"abstract":"<p><p>Dietary fiber interventions to modulate the gut microbiota have largely relied on isolated fibers or specific fiber sources. We hypothesized that fibers systematically blended could promote more health-related bacterial groups. Initially, pooled <i>in vitro</i> fecal fermentations were used to design dietary fiber mixtures to support complementary microbial groups related to health. Then, microbial responses were compared for the designed mixtures versus their single fiber components <i>in vitro</i> using fecal samples from a separate cohort of 10 healthy adults. The designed fiber mixtures outperformed individual fibers in supporting bacterial taxa across donors resulting in superior alpha diversity and unexpected higher SCFA production. Moreover, unique shifts in community structure and specific taxa were observed for fiber mixtures that were not observed for single fibers, suggesting a synergistic effect when certain fibers are put together. Fiber mixture responses were remarkably more consistent than individual fibers across donors in promoting several taxa, especially butyrate producers from the <i>Clostridium</i> cluster XIVa. This is the first demonstration of synergistic fiber interactions for superior support of a diverse group of important beneficial microbes consistent across people, and unexpectedly high SCFA production. Overall, harnessing the synergistic potential of designed fiber mixtures represents a promising and more efficacious avenue for future prebiotic development.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2442521"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863986","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}

{"title":"Development of a Caco-2-based intestinal mucosal model to study intestinal barrier properties and bacteria-mucus interactions.","authors":"Evelien Floor, Jinyi Su, Maitrayee Chatterjee, Elise S Kuipers, Noortje IJssennagger, Faranak Heidari, Laura Giordano, Richard W Wubbolts, Silvia M Mihăilă, Daphne A C Stapels, Yvonne Vercoulen, Karin Strijbis","doi":"10.1080/19490976.2024.2434685","DOIUrl":"https://doi.org/10.1080/19490976.2024.2434685","url":null,"abstract":"<p><p>The intestinal mucosal barrier is a dynamic system that allows nutrient uptake, stimulates healthy microbe-host interactions, and prevents invasion by pathogens. The mucosa consists of epithelial cells connected by cellular junctions that regulate the passage of nutrients covered by a mucus layer that plays an important role in host-microbiome interactions. Mimicking the intestinal mucosa for <i>in vitro</i> assays, particularly the generation of a mucus layer, has proven to be challenging. The intestinal cell-line Caco-2 is widely used in academic and industrial laboratories due to its capacity to polarize, form an apical brush border, and reproducibly grow into confluent cell layers in different culture systems. However, under normal culture conditions, Caco-2 cultures lack a mucus layer. Here, we demonstrate for the first time that Caco-2 cultures can form a robust mucus layer when cultured under air-liquid interface (ALI) conditions on Transwell inserts with addition of vasointestinal peptide (VIP) in the basolateral compartment. We demonstrate that unique gene clusters are regulated in response to ALI and VIP single stimuli, but the ALI-VIP combination treatment resulted in a significant upregulation of multiple mucin genes and proteins, including secreted MUC2 and transmembrane mucins MUC13 and MUC17. Expression of tight junction proteins was significantly altered in the ALI-VIP condition, leading to increased permeability to small molecules. Commensal <i>Lactiplantibacillus plantarum</i> bacteria closely associated with the Caco-2 mucus layer and differentially colonized the surface of the ALI cultures. Pathogenic <i>Salmonella enterica</i> were capable of invading beyond the mucus layer and brush border. In conclusion, Caco-2 ALI-VIP cultures provide an accessible and straightforward way to culture an <i>in vitro</i> intestinal mucosal model with improved biomimetic features. This novel <i>in vitro</i> intestinal model can facilitate studies into mucus and epithelial barrier functions and in-depth molecular characterization of pathogenic and commensal microbe-mucus interactions.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2434685"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876894","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}

{"title":"The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia.","authors":"Morgane M Thibaut, Martin Roumain, Edwige Piron, Justine Gillard, Axelle Loriot, Audrey M Neyrinck, Julie Rodriguez, Isabelle Massart, Jean-Paul Thissen, Joshua R Huot, Fabrizio Pin, Andrea Bonetto, Nathalie M Delzenne, Giulio G Muccioli, Laure B Bindels","doi":"10.1080/19490976.2025.2449586","DOIUrl":"10.1080/19490976.2025.2449586","url":null,"abstract":"<p><p>Alterations in bile acid profile and pathways contribute to hepatic inflammation in cancer cachexia, a syndrome worsening the prognosis of cancer patients. As the gut microbiota impinges on host metabolism through bile acids, the current study aimed to explore the functional contribution of gut microbial dysbiosis to bile acid dysmetabolism and associated disorders in cancer cachexia. Using three mouse models of cancer cachexia (the C26, MC38 and HCT116 models), we evidenced a reduction in the hepatic levels of several secondary bile acids, mainly taurodeoxycholic (TDCA). This reduction in hepatic TDCA occurred before the appearance of cachexia. Longitudinal analysis of the gut microbiota pinpointed an ASV, identified as <i>Xylanibacter rodentium</i>, as a bacterium potentially involved in the reduced production of TDCA. Coherently, stable isotope-based experiments highlighted a robust decrease in the microbial 7α-dehydroxylation (7α-DH) activity with no changes in the bile salt hydrolase (BSH) activity in cachectic mice. This approach also highlighted a reduced microbial 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 12α-hydroxysteroid dehydrogenase (12α-HSDH) activities in these mice. The contribution of the lower production of TDCA to cancer cachexia was explored <i>in vitro</i> and <i>in vivo</i>. <i>In vitro</i>, TDCA prevented myotube atrophy, whereas <i>in vivo</i> hepatic whole transcriptome analysis revealed that TDCA administration to cachectic mice improved the unfolded protein response and cholesterol homeostasis pathways. Coherently, TDCA administration reversed hepatic cholesterol accumulation in these mice. Altogether, this work highlights the contribution of the gut microbiota to bile acid dysmetabolism and the therapeutic interest of the secondary bile acid TDCA for hepatic cholesterol homeostasis in the context of cancer cachexia. Such discovery may prove instrumental in the understanding of other metabolic diseases characterized by microbial dysbiosis. More broadly, our work demonstrates the interest and relevance of microbial activity measurements using stable isotopes, an approach currently underused in the microbiome field.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2449586"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947812","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":"<i>Desulfovibrio vulgaris</i> flagellin exacerbates colorectal cancer through activating LRRC19/TRAF6/TAK1 pathway.","authors":"Yue Dong, Fanyi Meng, Jingyi Wang, Jingge Wei, Kexin Zhang, Siqi Qin, Mengfan Li, Fucheng Wang, Bangmao Wang, Tianyu Liu, Weilong Zhong, Hailong Cao","doi":"10.1080/19490976.2024.2446376","DOIUrl":"https://doi.org/10.1080/19490976.2024.2446376","url":null,"abstract":"<p><p>The initiation and progression of colorectal cancer (CRC) are intimately associated with genetic, environmental and biological factors. <i>Desulfovibrio vulgaris</i> (DSV), a sulfate-reducing bacterium, has been found excessive growth in CRC patients, suggesting a potential role in carcinogenesis. However, the precise mechanisms underlying this association remain incompletely understood. We have found <i>Desulfovibrio</i> was abundant in high-fat diet-induced <i>Apc</i>^<i>min/+</i> mice, and DSV, a member of <i>Desulfovibrio</i>, triggered colonocyte proliferation of germ-free mice. Furthermore, the level of DSV progressively rose from healthy individuals to CRC patients. Flagella are important accessory structures of bacteria, which can help them colonize and enhance their invasive ability. We found that <i>D. vulgaris</i> flagellin (DVF) drove the proliferation, migration, and invasion of CRC cells and fostered the growth of CRC xenografts. DVF enriched the epithelial-mesenchymal transition (EMT)-associated genes and characterized the facilitation of DVF on EMT. Mechanistically, DVF induced EMT through a functional transmembrane receptor called leucine-rich repeat containing 19 (LRRC19). DVF interacted with LRRC19 to modulate the ubiquitination of tumor necrosis factor receptor-associated factor (TRAF)6, rather than TRAF2. This interaction drove the ubiquitination of pivotal molecule TAK1, further enhancing its autophosphorylation and ultimately contributing to EMT. Collectively, DVF interacts with LRRC19 to activate the TRAF6/TAK1 signaling pathway, thereby promoting the EMT of CRC. These data shed new light on the role of gut microbiota in CRC and establish a potential clinical therapeutic target.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2446376"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881946","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}

{"title":"A modelling framework to characterize the impact of antibiotics on the gut microbiota diversity.","authors":"Carlos Olivares, Etienne Ruppé, Stéphanie Ferreira, Tanguy Corbel, Antoine Andremont, Jean de Gunzburg, Jeremie Guedj, Charles Burdet","doi":"10.1080/19490976.2024.2442523","DOIUrl":"https://doi.org/10.1080/19490976.2024.2442523","url":null,"abstract":"<p><p>Metagenomic sequencing deepened our knowledge about the role of the intestinal microbiota in human health, and several studies with various methodologies explored its dynamics during antibiotic treatments. We compared the impact of four widely used antibiotics on the gut bacterial diversity. We used plasma and fecal samples collected during and after treatment from healthy volunteers assigned to a 5-day treatment either by ceftriaxone (1 g every 24 h through IV route), ceftazidime/avibactam (2 g/500 mg every 8 h through IV route), piperacillin/tazobactam (1 g/500 mg every 8 h through IV route) or moxifloxacin (400 mg every 24 h through oral route). Antibiotic concentrations were measured in plasma and feces, and bacterial diversity was assessed by the Shannon index from 16S rRNA gene profiling. The relationship between the evolutions of antibiotic fecal exposure and bacterial diversity was modeled using non-linear mixed effects models. We compared the impact of antibiotics on gut microbiota diversity by simulation, using various reconstructed pharmacodynamic indices. Piperacillin/tazobactam was characterized by the highest impact in terms of intensity of perturbation (maximal [IQR] loss of diversity of 27.3% [1.9; 40.0]), while moxifloxacin had the longest duration of perturbation, with a time to return to 95% of baseline value after the last administration of 13.2 d [8.3; 19.1]. Overall, moxifloxacin exhibited the highest global impact, followed by piperacillin/tazobactam, ceftazidime/avibactam and ceftriaxone. Their AUC between day 0 and day 42 of the change of diversity indices from day 0 were, respectively, -13.2 Shannon unit.day [-20.4; -7.9], -10.9 Shannon unit.day [-20.4; -0.6] and -10.1 Shannon unit.day [-18.3; -4.6]. We conclude that antibiotics alter the intestinal diversity to varying degrees, both within and between antibiotics families. Such studies are needed to help antibiotic stewardship in using the antibiotics with the lowest impact on the intestinal microbiota.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2442523"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876887","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}

{"title":"Long-term yogurt intake and colorectal cancer incidence subclassified by <i>Bifidobacterium</i> abundance in tumor.","authors":"Satoko Ugai, Li Liu, Keisuke Kosumi, Hidetaka Kawamura, Tsuyoshi Hamada, Kosuke Mima, Kota Arima, Kazuo Okadome, Qian Yao, Kosuke Matsuda, Yuxue Zhong, Hiroki Mizuno, Andrew T Chan, Wendy S Garrett, Mingyang Song, Marios Giannakis, Edward L Giovannucci, Xuehong Zhang, Shuji Ogino, Tomotaka Ugai","doi":"10.1080/19490976.2025.2452237","DOIUrl":"10.1080/19490976.2025.2452237","url":null,"abstract":"<p><p>Evidence suggests a tumor-suppressive effect of the intake of yogurt, which typically contains <i>Bifidobacterium</i>. We hypothesized that long-term yogurt intake might be associated with colorectal cancer incidence differentially by tumor subgroups according to the amount of tissue <i>Bifidobacterium</i>. We utilized the prospective cohort incident-tumor biobank method and resources of two prospective cohort studies. Inverse probability weighted multivariable Cox proportional hazards regression was used to assess differential associations of yogurt intake with the incidence of colorectal carcinomas subclassified by the abundance of tumor tissue <i>Bifidobacterium</i>. During follow-up of 132,056 individuals, we documented 3,079 incident colorectal cancer cases, including 1,121 with available tissue <i>Bifidobacterium</i> data. The association between long-term yogurt intake and colorectal cancer incidence differed by <i>Bifidobacterium</i> abundance (P heterogeneity = 0.0002). Multivariable-adjusted hazard ratios (HRs) (with 95% confidence intervals) in individuals who consumed ≥2 servings/week (vs. <1 serving/month) of yogurt were 0.80 (0.50-1.28) for <i>Bifidobacterium</i>-positive tumor and 1.09 (0.81-1.46) for <i>Bifidobacterium</i>-negative tumor. This differential association was also observed in a subgroup analysis of proximal colon cancer (P heterogeneity = 0.018). Long-term yogurt intake may be differentially associated with the incidence of proximal colon cancer according to <i>Bifidobacterium</i> abundance, suggesting the antitumor effect of yogurt intake on the specific tumor subgroup.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2452237"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398876","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 gut microbiota: an emerging modulator of drug resistance in hepatocellular carcinoma.","authors":"Jiali Yao, Beifang Ning, Jin Ding","doi":"10.1080/19490976.2025.2473504","DOIUrl":"10.1080/19490976.2025.2473504","url":null,"abstract":"<p><p>Liver cancer is usually diagnosed at an advanced stage and is the third most common cause of cancer-related death worldwide. In addition to the lack of effective treatment options, resistance to therapeutic drugs is a major clinical challenge. The gut microbiota has recently been recognized as one of the key factors regulating host health. The microbiota and its metabolites can directly or indirectly regulate gene expression in the liver, leading to gut-liver axis dysregulation, which is closely related to liver cancer occurrence and the treatment response. Gut microbiota disturbance may participate in tumor progression and drug resistance through metabolite production, gene transfer, immune regulation, and other mechanisms. However, systematic reviews on the role of the gut microbiota in drug resistance in liver cancer are lacking. Herein, we review the relationships between the gut microbiota and the occurrence and drug resistance of hepatocellular carcinoma, summarize the emerging mechanisms underlying gut microbiota-mediated drug resistance, and propose new personalized treatment options to overcome this resistance.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2473504"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556252","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":"Gut microbiota alterations induced by Roux-en-Y gastric bypass result in glucose-lowering by enhancing intestinal glucose excretion.","authors":"Zhigang Ke, Zongshi Lu, Fan Li, Qingyuan Zhao, Xianhong Jiang, Zhihao Hu, Fang Sun, Zongcheng He, Yi Tang, Qing Li, Stefan van Oostendorp, Xiao Chen, Qiuyue He, Yong Wang, Zhiming Zhu, Weidong Tong","doi":"10.1080/19490976.2025.2473519","DOIUrl":"10.1080/19490976.2025.2473519","url":null,"abstract":"<p><p>Roux-en-Y gastric bypass (RYGB) results in glucose-lowering in patients with type 2 diabetes mellitus (T2DM) and may be associated with increased intestinal glucose excretion. However, the contribution of intestinal glucose excretion to glycemic control after RYGB and its underlying mechanisms are not fully elucidated. Here, we confirmed that intestinal glucose excretion significantly increased in obese rats after RYGB, which was negatively correlated with postoperative blood glucose levels. Moreover, we also found that the contribution of Biliopancreatic limb length, an important factor affecting glycemic control after RYGB, to the improvement of glucose metabolism after RYGB attributed to the enhancement of intestinal glucose excretion. Subsequently, we further determined through multiple animal models that intestinal glucose excretion is physiological rather than pathological and plays a crucial role in maintaining glucose homeostasis in the body. Finally, we employed germ-free mice colonized with fecal samples from patients and rats to demonstrate that enhanced intestinal glucose excretion after RYGB is directly modulated by the surgery-induced changes in the gut microbiota. These results indicated that the gut microbiota plays a direct causal role in the hypoglycemic effect of RYGB by promoting intestinal glucose excretion, which may provide new insights for developing gut microbiota-based therapies for T2DM.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2473519"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541370","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":"Novel insights into carbohydrate utilisation, antimicrobial resistance, and sporulation potential in <i>Roseburia intestinalis</i> isolates across diverse geographical locations.","authors":"Indrani Mukhopadhya, Jennifer C Martin, Sophie Shaw, Martin Gutierrez-Torrejon, Nikoleta Boteva, Aileen J McKinley, Silvia W Gratz, Karen P Scott","doi":"10.1080/19490976.2025.2473516","DOIUrl":"10.1080/19490976.2025.2473516","url":null,"abstract":"<p><p><i>Roseburia intestinalis</i> is one of the most abundant and important butyrate-producing human gut anaerobic bacteria that plays an important role in maintaining health and is a potential next-generation probiotic. We investigated the pangenome of 16 distinct strains, isolated over several decades, identifying local and time-specific adaptations. More than 50% of the genes in each individual strain were assigned to the core genome, and 77% of the cloud genes were unique to individual strains, revealing the high level of genome conservation. Co-carriage of the same enzymes involved in carbohydrate binding and degradation in all strains highlighted major pathways in carbohydrate utilization and reveal the importance of xylan, starch and mannose as key growth substrates. A single strain had adapted to use rhamnose as a sole growth substrate, the first time this has been reported. The ubiquitous presence of motility and sporulation gene clusters demonstrates the importance of these phenotypes for gut survival and acquisition of this bacterium. More than half the strains contained functional, potentially transferable, tetracycline resistance genes. This study advances our understanding of the importance of <i>R. intestinalis</i> within the gut ecosystem by elucidating conserved metabolic characteristics among different strains, isolated from different locations. This information will help to devise dietary strategies to increase the abundance of this species providing health benefits.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2473516"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633873","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 crystal structure of the toxin EspC from enteropathogenic <i>Escherichia coli</i> reveals the mechanism that governs host cell entry and cytotoxicity.","authors":"Akila U Pilapitiya, Lilian Hor, Jing Pan, Lakshmi C Wijeyewickrema, Robert N Pike, Denisse L Leyton, Jason J Paxman, Begoña Heras","doi":"10.1080/19490976.2025.2483777","DOIUrl":"10.1080/19490976.2025.2483777","url":null,"abstract":"<p><p>Enteropathogenic <i>E. coli</i> (EPEC) is a significant cause of diarrhea, leading to high infant mortality rates. A key toxin produced by EPEC is the EspC autotransporter, which is regulated alongside genes from the locus of enterocyte effacement (LEE), which collectively result in the characteristic attaching and effacing lesions on the intestinal epithelium. In this study, we present the crystal structure of the EspC passenger domain (α^EspC) revealing a toxin comprised a serine protease attached to a large β-helix with additional subdomains. Using various modified EspC expression constructs, alongside type III secretion system-mediated cell internalization assays, we dissect how the α^EspC structural features enable toxin entry into the intestinal epithelium to cause cell cytotoxicity.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2483777"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752385","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}