Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice - Centre de recherche Saint-Antoine - UMR S938
Journal Articles Nature Communications Year : 2024

Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice

Mouna Chajadine
  • Function : Author
Ludivine Laurans
  • Function : Author
Tobias Radecke
  • Function : Author
Nirmala Mouttoulingam
  • Function : Author
Rida Al-Rifai
Emilie Bacquer
  • Function : Author
Clara Delaroque
  • Function : Author
Héloïse Rytter
  • Function : Author
Marius Bredon
  • Function : Author
Camille Knosp
  • Function : Author
José Vilar
Coralie Fontaine
  • Function : Author
Nadine Suffee
Marie Vandestienne
Bruno Esposito
  • Function : Author
Julien Dairou
  • Function : Author
Jean Marie Launay
  • Function : Author
Jacques Callebert
  • Function : Author
Alain Tedgui
Hafid Ait-Oufella
Benoit Chassaing
Soraya Taleb
  • Function : Correspondent author
  • PersonId : 1074944

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Abstract

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.
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hal-04670622 , version 1 (12-08-2024)

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Mouna Chajadine, Ludivine Laurans, Tobias Radecke, Nirmala Mouttoulingam, Rida Al-Rifai, et al.. Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice. Nature Communications, 2024, 15 (1), pp.6390. ⟨10.1038/s41467-024-50807-x⟩. ⟨hal-04670622⟩
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