An obesogenic diet increases atherosclerosis through promoting microbiota dysbiosis-induced gut lymphocyte trafficking into the periphery

• DOI: 10.1016/j.celrep.2023.113350
• Publication Date: 2023-10-31T14:14:30Z
• Authors: Ludivine Laurans; Nirmala Mouttouli...; Mouna Chajadine; Aonghus Lavelle; Marc Diedisheim; Emilie Bacquer; Laura Creusot; Nadine Suffee; Bruno Esposito; Nada Joe Melhem; Wilfried Le Goff; Yacine Haddad; Jean-Louis Paul; Dominique Rainteau; Alain Tedgui; Hafid Ait-Oufella; Laurence Zitvogel; Harry Sokol; Soraya Taleb
• Keywords: Dysbiosis; Addressin; Mesenteric lymph nodes

Although high-fat diet (HFD)-induced gut microbiota dysbiosis is known to affect atherosclerosis, the underlying mechanisms remain to be fully explored. Here, we show that the progression of atherosclerosis depends on a gut microbiota shaped by an HFD but not a high-cholesterol (HC) diet and, more particularly, on low fiber (LF) intake. Mechanistically, gut lymphoid cells impacted by HFD- or LF-induced microbiota dysbiosis highly proliferate in mesenteric lymph nodes (MLNs) and migrate from MLNs to the periphery, which fuels T cell accumulation within atherosclerotic plaques. This is associated with the induction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) within plaques and the presence of enterotropic lymphocytes expressing β7 integrin. MLN resection or lymphocyte deficiency abrogates the pro-atherogenic effects of a microbiota shaped by LF. Our study shows a pathological link between a diet-shaped microbiota, gut immune cells, and atherosclerosis, suggesting that a diet-modulated microbiome might be a suitable therapeutic target to prevent atherosclerosis.