Berberine improves lipid levels, vascular function, and gut microbial-dependent metabolites in stable coronary artery disease patients.

Abstract

Berberine (BBR) has been demonstrated to exert cardiovascular protective effects by regulating lipids and ameliorating inflammation. Recent studies reported the interaction between BBR and gut microbiota in various metabolic diseases due to its low bioavailability. However, few studies examine the effect of BBR on the gut microbiota in coronary artery disease (CAD) individuals. We hence conducted a parallel-controlled, regularly visited clinical trial with 23 stable CAD patients who recently underwent percutaneous coronary intervention and completed a 12-week BBR ± standard therapy treatment. The BBR intervention was associated with a directional improvement in endothelial function, enhanced levels of low-density lipoprotein cholesterol (LDL-C), and a reduction in circulating inflammatory mediators (IL-1α, IL-17, MCP-1, MIP-1β, and VEGF). Using metagenomics and metabolomic studies, we identified that bacterial signatures varied significantly with gradually increasing doses of BBR. These results showed that a specific group of short-chain fatty acid (SCFA)-producing bacteria, mainly Ruminococcus sp., Roseburia sp., and Anaerostipes hadrus, were elevated following the BBR intervention, which was also negatively correlated with inflammatory factors. Notably, regardless of the background standard therapy, BBR reshaped gut-microbiota-encoded aromatic amino acid catabolism: it selectively enriched the microbial L-dopa, 3-hydroxyphenylacetic acid, and phenylpropionic acid branches, which were anchored by increased abundances of dopamine β-monooxygenase, porA, and acdA genes. Overall, we investigated the role of BBR in regulating microbial metabolic alterations and vascular function. Targeted restoration of the gut microbiota may present a novel ecological approach for managing cardiovascular disease.