The Gut-Heart Axis in Cardiovascular Disease: Microbial Metabolites, Mediterranean and Traditional Turkish Dietary...

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality globally. Increasing evidence identifies the gut microbiota as one of the major regulators of cardiovascular health, leading to the concept of the gut-heart axis. Metabolites from microbiota serve as key mediators linking intestinal microbial activity with vascular and metabolic processes. This comprehensive narrative review was conducted using PubMed and Scopus databases, focusing on studies published between 2015 and 2025, along with selected seminal studies, to show the role of gut microbiota and its metabolites in CVD. Microbial metabolites exert various important and often opposing effects on cardiovascular physiology. Trimethylamine N-oxide (TMAO), derived from dietary choline and carnitine metabolism, promotes atherosclerosis through endothelial dysfunction, inflammation, foam cell formation, impaired cholesterol transport, and enhanced platelet reactivity. In contrast, short-chain fatty acids (SCFAs), produced by microbial fermentation of dietary fibers, exert protective effects by reducing inflammation, improving endothelial function, and maintaining intestinal barrier integrity by G protein coupled receptor activation and histone deacetylase inhibition. Disruption of gut barrier function facilitates lipopolysaccharide translocation, contributing to systemic inflammation and cardiometabolic risk. Bile acids further modulate cardiovascular processes through FXR and TGR5 signaling pathways; this influences lipid metabolism and inflammatory responses. Dietary patterns, including the Mediterranean diet and dietary diversity in Türkiye, play a central role in shaping microbiota composition and metabolite balance. The gut-heart axis represents a complex and dynamic process in which microbiota-derived metabolites exert a critical influence on cardiovascular health and disease. Modulation of the gut microbiome through dietary interventions, microbiota-targeted therapies, and emerging personalized strategies offers promising avenues for the prevention and management of CVDs. Future research should focus on microbiome-based precision approaches and large-scale clinical validation to facilitate translation into clinical practice.