Obesogenic diet increases atherosclerosis through promoting microbiota dysbiosis-induced gut lymphocyte trafficking into periphery - 25/06/24
, Mouna Chajadine a, Emilie Bacquer a, Aonghus Lavelle b, Bruno Esposito c, Alain Tedgui d, Hafid Ait Oufella d, Lawrence Zitvogel e, Harry Sokol b, Soraya Taleb f
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Résumé |
Introduction |
Despite novel therapies, cardiovascular diseases such as atherosclerosis remain the leading cause of death worldwide. Several factors such as diet, particularly, the obesogenic high-fat diet (HFD), could alter gut microbiota and systemic inflammation, which are known to impact atherosclerosis. However, the causal links remain to be established.
Objective |
We investigated underlying mechanisms through which gut microbiota shaped by an HFD influences the development of atherosclerosis.
Method |
We used the low-density lipoprotein knock-out (ldlr-/-) mice that develop atherosclerosis when fed a high-cholesterol (HC) diet. To study the specific role of gut microbiota shaped by the diet, we performed fecal microbiota transplantation (FMT). Microbiota was harvested from ldlr-/- mice fed different diets: chow diet (CD), HC diet, HFD, combined HFD+HC, or low fiber (LF) diet. This last diet has a low content of fibers equivalent to HFD. All, microbiota-recipient ldlr-/- mice were fed the same atherogenic diet. In addition, some microbiota-donor mice were supplemented with soluble fibers such as fructooligosaccharides (FOS). Microbiota was analyzed using 16S rRNA sequencing from fecal samples. Harvested hearts and aortas were used to analyze atheromatous plaques and plaques inflammatory contents.
Results |
Our results show that gut microbiota shaped by HFD but not HC diet compared to CD, led to a significant increase in atherosclerotic plaques along with an increase in T cell accumulation within the plaques. Moreover, the pro-atherogenic effect of HFD-shaped microbiota was related to LF intake as evidenced by fiber supplementation that could reverse HFD-shaped microbiota effects. Furthermore, our work reveals a significant increase in gut immune cell trafficking mostly lymphocytes, imprinted by HFD- and LF-shaped microbiota, from the gut to the periphery, which exerts a pro-atherogenic role (Fig. 1).
Conclusion |
Our work unravels the missing pathological link between the HFD, particularly due to a low fiber level, gut microbiota dysbiosis, gut immune cell trafficking, and atherosclerosis.
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Vol 117 - N° 6-7S
P. S162 - juin 2024 Retour au numéro
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