Deciphering microbiota–host interactions through a multiomics approach: influence of prebiotics and Red Yeast Rice in a murine model of atherosclerosis

Atherosclerosis (AS), a chronic low-grade inflammatory disorder affecting large and medium-sized arteries, represents one of the principal causes of cardiovascular morbidity and mortality worldwide. Despite major advances in pharmacological management, there remains a critical need for complementary strategies that can target early pathogenic mechanisms and support vascular health. Recent evidence has identified gut microbiota dysbiosis as a key contributor to AS development and progression. Microbial-derived metabolites such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS) have been shown to exert opposing influences on vascular inflammation and lipid metabolism. Modulating the gut microbiota through nutritional or nutraceutical interventions (such as prebiotics) has therefore emerged as a promising approach to restore microbial balance and promote cardioprotective effects. In this context, the present study aimed to investigate the impact of a prebiotic formulation, administered alone or in combination with red yeast rice (RYR) extract, one of the most used botanicals for AS patients, on atherosclerosis development in ApoE⁻/⁻ micefed with a high-fat diet. Through an integrated multi-omic strategy encompassing proteomics, metaproteomics, and metagenomics, combined with biochemical and vascular assessments, the principal objective has been to unravel the molecular mechanisms linking microbiota modulation to systemic metabolic and vascular outcomes. Ultimately, this study aimed to identify differentially expressed proteins and microbial shifts that could serve as potential biomarkers or therapeutic targets for atherosclerosis, paving the way for microbiota-centered nutraceutical strategies in cardiovascular prevention and personalized medicine.