<i>Clostridium sporogenes</i> -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 <i>Clostridium sporogenes</i> 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 <i>C. sporogenes</i> (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of <i>Il22</i> gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3<sup>+</sup> 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. <i>C. sporogenes</i>-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 <i>C. sporogenes</i> enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified <i>C. sporogenes</i> as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).
Authors
- Wolfgang Andreas Nockher
- Wilhelm Bertrams (ORCID: https://orcid.org/0000-0002-0180-2529)
- Kai Binder
- Burkhard Schütz (ORCID: https://orcid.org/0000-0003-4473-1959)
- Sarah Winterberg
- Anja A. Kühl (ORCID: https://orcid.org/0000-0003-2293-5387)
- Britta Siegmund (ORCID: https://orcid.org/0000-0002-0055-958X)
- Hanna Leister
- Isabelle Bekeredjian‐Ding (ORCID: https://orcid.org/0000-0001-6646-5888)
- Rossana Romero (ORCID: https://orcid.org/0000-0002-4319-236X)
- Ulrich Steinhoff (ORCID: https://orcid.org/0000-0003-2141-7756)
- Anne Hellhund-Zingel
- Ralf Kinscherf
- Maik Luu (ORCID: https://orcid.org/0000-0003-2843-3919)
- Hartmann Raifer (ORCID: https://orcid.org/0000-0002-7253-4752)
- Anna-Lena Ruppert
- Jelena Pesek
- Bernd Schmeck (ORCID: https://orcid.org/0000-0002-2767-3606)
- Alesia Walker (ORCID: https://orcid.org/0000-0002-1477-2023)
- Alexander Visekruna (ORCID: https://orcid.org/0000-0002-5207-9545)
- R. Verena Taudte (ORCID: https://orcid.org/0000-0003-4617-6063)
- Bernhard Watzer
- Aleksandra Lopez Krol (ORCID: https://orcid.org/0009-0002-3151-9748)
- Felix F. Krause
- Stephan Göttig
- Kira Mangold
Institutions
- Goethe University Frankfurt (DE)
- Philipps University of Marburg (DE)
- Helmholtz Zentrum München (DE)
- Humboldt-Universität zu Berlin (DE)
- Universitätsklinikum Würzburg (DE)
- German Center for Lung Research (DE)
- Universities of Giessen and Marburg Lung Center (DE)
- University Hospital Frankfurt (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Institute of Medical Microbiology and Hygiene (DE)
- Freie Universität Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Gut Microbes
- Published
- 2024-10-14
- DOI
- https://doi.org/10.1080/19490976.2024.2412669
- Citations
- 42
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 9.82
Funders
- Philipps-Universität Marburg
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Hessisches Ministerium für Wissenschaft und Kunst