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 and a recent study on secondary prevention of cardiovascular disease, a potential benefit of the Mediterranean diet after an acute coronary syndrome is expected. 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 was 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 was to decipher the interplays among diet, microbiota, immunity and metabolism responsible for the observed effects. To achieve those objectives we have conducted a randomized mechanistic clinical trial , MEDIMACS (n=100). A 72% of the patients completed the 12 months follow-up, and 50% underwent the second hemodynamic study. Although data are under analysis, relevant changes from baseline to 12-month follow-up have been identified in plaque characteristics and composition, anthropometric measures and nutritional composition of the diet. In the same line, relevant changes from baseline to 12-month follow-up have be detected in microbiota composition  The genus Ruminococcus, Intestinimonas, Oscillospiraceae, Faecalibacterium, Eubacterium showed the most relevant gut abundance changes over time. In addition, T CD4+immune cell populations, serum cytokines (IL6, TNFB, among others) and several lipoproteins, amino acids and metabolites, including TMAO, showed significant changes over time. Final integration analysis will provide us of valuable insights to identify potential microbiome-based therapeutic targets for coronary artery disease.

The current proposal consisted of original research on a diet intervention for secondary prevention in patients who have suffered acute coronary syndrome-Clinical Trial. This study will provide valuable insights to identify potential microbiome therapeutic targets for coronary artery disease. Final data analyses conditional on the final primary end-point analysis are in course.

Primary endpoint of the clinical trial is currently under analysis, but relevant changes from baseline to 12-month follow-up have been identified in plaque characteristics and composition (fibrous cap thickness, area lumen, elastic membrane, plaque burden and lumen, vessel and plaque volumes). 

The well-controlled Mediterranean diet positively impacts on anthropometric and biochemical parameters closely linked to cardiovascular health.  Relevant changes over time have been detected on weight, waist and hip measures and changes in nutritional composition of the diet such as trans-fatty acids, Omega3 and Omega6. Changes that are expected to be linked on arm intervention (High-Intensity MedDiet).

Relevant changes over time have been detected on gut microbiota abundance. The genus Ruminococcus, Intestinimonas, Oscillospiraceae, Faecalibacterium, Eubacterium,Tyzzerella, Paraprevotella, Fusicatenibacter, Lachnospira and Odoribacter showed the most relevant abundance changes over time. Final results for microbiota changes conditional on arm intervention (High-Intensity MedDiet) will be further analysed.

The well-controlled Mediterranean diet significantly impacts on immune response. The T CD4+ cell population (Th1,Th2,Th17,Th1/Th17 and Treg subtypes) showed the largest differences over time. Serum cytokines and inflammation-related proteins such as IL6 ,Flt3L, HGF, uPA, TWEAK, CD244, IL-15RA, CCL11, TNFB and MMP-10 showed the most relevant changes over time. In the same sense, changes metabolite profiles in serum, urine and faeces have been identified over time. Most relevant changes were detected for Free cholesterol in LDL, Phospholipids in VLDL, apolipoliprotein-B, Oxaloacetic acid and Taurine.  Changes that maybe attribute to arm intervention (High-Intensity MedDiet) and will be further analysed

The interplay between diet-microbiota mediated by immune system and metabolism changes is currently under analysis., which may explain, at least in part, the positive impact of Mediterranean diet on disease progression.