The Role of the Gut Microbiome in the Relationship Between the Mediterranean Diet and Cardiovascular Disease Risk

Abstract

This review critically summarizes evidence linking the Mediterranean diet, gut microbiome, microbial metabolites, and cardiovascular disease risk, with emphasis on the shift from microbial taxonomy to functional pathways, multiomic integration, and translation to precision nutrition. Mediterranean diet adherence is associated with enrichment of fiber-degrading and short-chain fatty acid-producing taxa, greater microbial capacity for polysaccharide degradation, and more favorable bile acid, phenolic, lipid, and inflammatory profiles. Evidence from randomized trials and prospective cohort studies suggests that microbiome remodeling may partly mediate or modify the effects of the Mediterranean diet on adiposity, insulin resistance, lipid metabolism, inflammation, and cardiometabolic risk. However, effects are heterogeneous, global diversity metrics are inconsistent, and most studies rely on surrogate outcomes rather than incident cardiovascular events. The gut microbiome is a plausible mediator and modifier of Mediterranean diet-related cardiovascular protection, but it is not yet a validated clinical target. Future research should prioritize longitudinal multiomic studies with repeated measures, standardized analytical pipelines, externally validated biomarkers, and pragmatic trials testing whether microbiome-informed Mediterranean diet counseling improves adherence, cardiometabolic profiles, and cardiovascular outcomes.