An obesogenic diet increases atherosclerosis through promoting microbiota dysbiosis-induced gut lymphocyte trafficking into the periphery
Ludivine Laurans, Nirmala Mouttoulingam, 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
Abstract
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.