Association of Butyrate Supplementation with Cardiovascular Disease:A Narrative Review

Cardiovascular diseases (CVDs) have long been a significant source of the global disease burden and a leading cause of death and disability. In recent years, the precise microbiome modulation of the gut has made remarkable progress as a new strategy for treating CVDs, especially its production of short-chain fatty acids, the primary way the gut flora affects the organism. Butyrate, one of the critical metabolites of short-chain fatty acids, butyrate uniquely restores intestinal barrier function, suppresses systemic inflammation, promotes immune tolerance, and regulates energy metabolism while antagonizing the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO) via the gut-heart axis. Preclinical studies consistently show that butyrate supplementation mitigates heart failure (HF), atherosclerosis, myocardial infarction, hypertrophic cardiomyopathy, hypertension, and cancer-related cardiac injury, and concurrently ameliorates metabolic syndrome, dyslipidaemia, and hyperglycaemia. However, clinical translation is currently hampered by a lack of large-scale human randomized controlled trials (RCTs) and an insufficient understanding of human dose-response relationships. This review synthesizes knowledge on butyrate's cardiovascular actions, details the underlying mechanisms, and highlights critical evidence gaps to inform future translational research.