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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 aci...

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Main Authors: Krause, Felix F., Mangold, Kira I., Ruppert, Anna-Lena, Leister, Hanna, Hellhund-Zingel, Anne, Lopez Krol, Aleksandra, Pesek, Jelena, Watzer, Bernhard, Winterberg, Sarah, Raifer, Hartmann, Binder, Kai, Kinscherf, Ralf, Walker, Alesia, Nockher, Wolfgang A., Taudte, R. Verena, Bertrams, Wilhelm, Schmeck, Bernd, Kühl, Anja A., Siegmund, Britta, Romero, Rossana, Luu, Maik, Göttig, Stephan, Bekeredjian-Ding, Isabelle, Steinhoff, Ulrich, Schütz, Burkhard, Visekruna, Alexander
Format: Article
Language:English
Published: Philipps-Universität Marburg 2024
Subjects:
Medizin
Colitis
commensal bacteria; indole-3-propionate; microbial metabolites
Medical sciences Medicine
Online Access:PDF Full Text
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Summary: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).
Item Description:Gefördert durch den Open-Access-Publikationsfonds der UB Marburg.
DOI:10.1080/19490976.2024.2412669

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