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.