Gut microbiota-derived metabolites in cardiovascular disease: mechanisms, disease-specific roles, and translational opportunities.

Cardiovascular disease remains the leading cause of global morbidity and mortality and arises from complex interactions among metabolic dysregulation, inflammation, thrombosis, and vascular dysfunction. In recent years, the gut microbiota has emerged as an important regulator of cardiovascular pathophysiology, largely through the production of bioactive metabolites that act on distant organs. This review summarizes the major classes of gut microbiota-derived metabolites involved in cardiovascular disease, with particular emphasis on trimethylamine N-oxide, short-chain fatty acids, phenylacetylglutamine, bile acids, and tryptophan-derived metabolites. We discuss how these metabolites influence endothelial dysfunction, immune activation, lipid handling, platelet reactivity, cardiac remodeling, gut barrier integrity, and blood pressure regulation through interconnected signaling pathways. We further examine their disease-specific relevance in atherosclerosis, heart failure, hypertension, and coronary artery disease/acute coronary syndrome. In addition, we evaluate current translational strategies targeting microbial metabolism, including dietary modulation, probiotics and prebiotics, fecal microbiota transplantation, and selective inhibition of microbial enzymes. Rather than viewing individual metabolites as uniformly harmful or protective, we propose that cardiovascular risk is better understood as the net consequence of interacting microbial metabolic pathways within specific host contexts. This metabolite-centered framework may help refine biomarker development, risk stratification, and pathway-guided interventions in cardiovascular medicine.