Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice.

Autor: Chajadine M; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Laurans L; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Radecke T; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Mouttoulingam N; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Al-Rifai R; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Bacquer E; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Delaroque C; Microbiome-Host interactions, Institut Pasteur, Université Paris Cité, INSERM U1306, Paris, France.; INSERM U1016, Team 'Mucosal microbiota in chronic inflammatory diseases', CNRS UMR10 8104, Université Paris Cité, Paris, France., Rytter H; Microbiome-Host interactions, Institut Pasteur, Université Paris Cité, INSERM U1306, Paris, France.; INSERM U1016, Team 'Mucosal microbiota in chronic inflammatory diseases', CNRS UMR10 8104, Université Paris Cité, Paris, France., Bredon M; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012, Paris, France.; Paris Centre for Microbiome Medicine (PaCeMM) FHU, Paris, France., Knosp C; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Vilar J; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Fontaine C; Inserm U1297, Institut des Maladies Métaboliques et Cardiovasculaires, Université de Toulouse, BP 84225, 31 432 Toulouse cedex 04, cedex, France., Suffee N; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Vandestienne M; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Esposito B; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Dairou J; Université Paris cité, CNRS, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, F-75006 Paris, France. 45 rue des Saints Pères, 75006, Paris, France., Launay JM; Assistance Publique Hôpitaux de Paris, Service de Biochimie and INSERM U942, Hôpital Lariboisière, Paris, France., Callebert J; Assistance Publique Hôpitaux de Paris, Service de Biochimie and INSERM U942, Hôpital Lariboisière, Paris, France., Tedgui A; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Ait-Oufella H; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France., Sokol H; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012, Paris, France.; Paris Centre for Microbiome Medicine (PaCeMM) FHU, Paris, France.; Université Paris-Saclay, INRAe, AgroParisTech, Micalis institute, Jouy-en-Josas, France Université Paris-Saclay, INRAe, AgroParisTech, Micalis institute, Jouy-en-Josas, France., Chassaing B; Microbiome-Host interactions, Institut Pasteur, Université Paris Cité, INSERM U1306, Paris, France.; INSERM U1016, Team 'Mucosal microbiota in chronic inflammatory diseases', CNRS UMR10 8104, Université Paris Cité, Paris, France., Taleb S; Université Paris Cité, Inserm, PARCC, F-75015, Paris, France. soraya.taleb@inserm.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 29; Vol. 15 (1), pp. 6390. Date of Electronic Publication: 2024 Jul 29.
DOI: 10.1038/s41467-024-50807-x
Abstrakt: Tryptophan (Trp) is an essential amino acid, whose metabolism is a key gatekeeper of intestinal homeostasis. Yet, its systemic effects, particularly on atherosclerosis, remain unknown. Here we show that high-fat diet (HFD) increases the activity of intestinal indoleamine 2, 3-dioxygenase 1 (IDO), which shifts Trp metabolism from the production of microbiota-derived indole metabolites towards kynurenine production. Under HFD, the specific deletion of IDO in intestinal epithelial cells leads to intestinal inflammation, impaired intestinal barrier, augmented lesional T lymphocytes and atherosclerosis. This is associated with an increase in serotonin production and a decrease in indole metabolites, thus hijacking Trp for the serotonin pathway. Inhibition of intestinal serotonin production or supplementation with indole derivatives alleviates plaque inflammation and atherosclerosis. In summary, we uncover a pivotal role of intestinal IDO in the fine-tuning of Trp metabolism with systemic effects on atherosclerosis, paving the way for new therapeutic strategies to relieve gut-associated inflammatory diseases.
(© 2024. The Author(s).)
Databáze: MEDLINE
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