Abstract
Statins are cornerstone therapies for cardiovascular disease prevention, yet adherence and efficacy remain suboptimal. Emerging evidence links gut microbiome composition to statin pharmacokinetics and metabolic effects. Enterotype-based dietary interventions may personalize microbiome modulation to enhance statin response. This randomized controlled trial investigated whether enterotype-guided dietary recommendations improve statin adherence and lipid-lowering efficacy compared to standard dietary advice. 320 adults with hypercholesterolemia initiating statin therapy were stratified into three dominant enterotypes (Prevotella, Bacteroides, Ruminococcus) via 16S rRNA sequencing and randomly assigned to enterotype-specific dietary interventions or generic heart-healthy diet. At 12 weeks, the intervention group showed significantly higher statin adherence (92% vs 78%, p<0.001) and greater LDL-cholesterol reduction (-52% vs -41%, p=0.003) compared to the control. Enterotype-specific responses were observed: Prevotella-dominant participants benefited most from high-fiber diets, while Bacteroides-dominant participants responded better to polyphenol-rich interventions. Gut microbiome diversity increased significantly in the intervention group. These findings suggest that enterotype-guided dietary personalization holds promise for improving statin outcomes and warrant further investigation in larger, longer-term studies.