Coronary atherosclerosis is a leading cause of mortality and disability worldwide. Continuous efforts are needed to improve secondary prevention and understand the mechanism underlying disease progression. Based on primary prevention trials, a potential benefit of the Mediterranean diet after an acute coronary syndrome can be anticipated. The integrated microbiome-mediated/immunologic and metabolic pathways by which the Mediterranean diet modifies cardiovascular risk remain mostly unknown. Intestinal and oral dysbiosis is involved in the pathogenesis of atherosclerosis and microbiome dynamics may account for some of the observed benefits of Mediterranean diet.Our first objective is to evaluate the effects of a well-controlled Mediterranean diet intervention on atherosclerotic plaque vulnerability and coronary endothelial dysfunction after an episode of acute coronary syndrome. The second objective is to decipher the interplays among diet, microbiota, immunity and metabolism responsible for the observed effects. We propose a randomized mechanistic clinical trial, using state-of-the-art efficacy read-outs. The multidisciplinary consortium includes highly experienced cardiologists, nutritionists and experts in translational research in immunology, microbiomics, genomics, proteomics, metabolomics and metagenomics. This study will provide valuable insights to identify potential microbiome therapeutic targets for coronary artery disease.

The current proposal consists of original research on a diet intervention for secondary prevention in patients who have suffered acute coronary syndrome. Moreover, the proposal consists of original research using innovative joint phenotypic, genomic, metagenomics, metabolomic and proteomic approaches for evaluation of coronary physiology, microbiota, the immune system and protein characterization of the host and his/her microbiota. Emphasis shall be placed on mechanism deciphering. The integration of diet, microbiota and cardiovascular disease using state-of-the-art omics and imaging methodology is entirely novel.

The MEDIMACS project is based on a randomized mechanistic clinical trial, using state-of-the-art efficacy read-outs. The multidisciplinary consortium includes highly experienced cardiologists, nutritionists and experts in translational research in immunology, microbiomics, genomics, proteomics, metabolomics and metagenomics. The integration of the clinical and mechanistic objectives will provide valuable insights to identify causal relationship of microbiome targets for coronary artery disease.