Microbiome and atherosclerosis: hype or future therapeutic target?

Abstract

From 2010 to 2025, evidence increasingly identifies the gut microbiome, microbial dysbiosis, trimethylamine-N-oxide (TMAO), and short-chain fatty acids (SCFAs) as modulators of atherosclerosis and cardiovascular disease. We conducted a narrative review of literature retrieved from PubMed, Scopus, and the Clinical Trials Registry-India (CTRI), covering studies published between January 2010 and March 2025. A total of 103 primary studies (animal, n=15; human cohort, n=28; mechanistic, n=22; randomized controlled trials, n=38) and 10 ongoing clinical trials were reviewed. Germ-free and antibiotic-treated murine models support a role for TMA-producing microbial communities in plaque formation, whereas SCFA-producing communities attenuate inflammation and atherogenesis. In humans, elevated TMAO levels are associated with a 2-5-fold higher risk of major adverse cardiovascular events (MACE), although causal inference remains limited. Probiotics, synbiotics, dietary interventions, and fecal microbiota transplantation may improve TMAO, LDL cholesterol, and inflammatory markers, but definitive reductions in cardiovascular events have not been demonstrated. Overall, microbiome-targeted strategies remain promising but require large, diverse clinical trials to establish causality and clinical benefit.