Institute for Medical Microbiology and Hygiene, Philipps-University, Marburg, Germany
Ralf Kinscherf
Institute of Anatomy and Cell Biology, Philipps-University, Marburg, Germany
Alesia Walker
Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum, München, Germany
Wolfgang A. Nockher
Core Facility for Metabolomics, Department of Medicine, Philipps-University, Marburg, Germany
R. Verena Taudte
Core Facility for Metabolomics, Department of Medicine, Philipps-University, Marburg, Germany
Wilhelm Bertrams
Institute for Lung Research, Philipps-University, Marburg, Germany
Bernd Schmeck
Institute for Lung Research, Philipps-University, Marburg, Germany
Anja A. Kühl
iPATH.Berlin, Core Unit of Charité-Universitätsmedizin Berlin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Britta Siegmund
Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
Rossana Romero
Institute for Medical Microbiology and Hygiene, Philipps-University, Marburg, Germany
Maik Luu
Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany
Stephan Göttig
Institute of Medical Microbiology and Infection Control, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
Isabelle Bekeredjian-Ding
Institute for Medical Microbiology and Hygiene, Philipps-University, Marburg, Germany
Ulrich Steinhoff
Institute for Medical Microbiology and Hygiene, Philipps-University, Marburg, Germany
Burkhard Schütz
Institute of Anatomy and Cell Biology, Philipps-University, Marburg, Germany
Alexander Visekruna
Institute for Medical Microbiology and Hygiene, Philipps-University, Marburg, Germany
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).
