Felix F Krause,Kira I Mangold,Anna-Lena Ruppert,Hanna Leister,Anne Hellhund-Zingel,Aleksandra Lopez Krol,Jelena Pesek,Bernhard Watzer,Sarah Winterberg,Hartmann Raifer,Kai Binder,Ralf Kinscherf,Alesia Walker,Wolfgang A Nockher,R Verena Taudte,Wilhelm Bertrams,Bernd Schmeck,Anja A Kühl,Britta Siegmund,Rossana Romero,Maik Luu,Stephan Göttig,Isabelle Bekeredjian-Ding,Ulrich Steinhoff,Burkhard Schütz,Alexander Visekruna
{"title":"源于孢子梭菌的代谢物可保护小鼠免受结肠炎的侵袭。","authors":"Felix F Krause,Kira I Mangold,Anna-Lena Ruppert,Hanna Leister,Anne Hellhund-Zingel,Aleksandra Lopez Krol,Jelena Pesek,Bernhard Watzer,Sarah Winterberg,Hartmann Raifer,Kai Binder,Ralf Kinscherf,Alesia Walker,Wolfgang A Nockher,R Verena Taudte,Wilhelm Bertrams,Bernd Schmeck,Anja A Kühl,Britta Siegmund,Rossana Romero,Maik Luu,Stephan Göttig,Isabelle Bekeredjian-Ding,Ulrich Steinhoff,Burkhard Schütz,Alexander Visekruna","doi":"10.1080/19490976.2024.2412669","DOIUrl":null,"url":null,"abstract":"Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"23 1","pages":"2412669"},"PeriodicalIF":12.2000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clostridium sporogenes-derived metabolites protect mice against colonic inflammation.\",\"authors\":\"Felix F Krause,Kira I Mangold,Anna-Lena Ruppert,Hanna Leister,Anne Hellhund-Zingel,Aleksandra Lopez Krol,Jelena Pesek,Bernhard Watzer,Sarah Winterberg,Hartmann Raifer,Kai Binder,Ralf Kinscherf,Alesia Walker,Wolfgang A Nockher,R Verena Taudte,Wilhelm Bertrams,Bernd Schmeck,Anja A Kühl,Britta Siegmund,Rossana Romero,Maik Luu,Stephan Göttig,Isabelle Bekeredjian-Ding,Ulrich Steinhoff,Burkhard Schütz,Alexander Visekruna\",\"doi\":\"10.1080/19490976.2024.2412669\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. 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Clostridium sporogenes-derived metabolites protect mice against colonic inflammation.
Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).
期刊介绍:
The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more.
Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.