The Gut-Cholesterol Axis: How Microbiota Imbalance Contributes to Hypercholesterolemia

Abstract

The human gut microbiota, a complex ecosystem of trillions of microorganisms, plays a crucial and previously underappreciated role in regulating host cholesterol homeostasis. A growing body of evidence indicates that a disruption in this microbial community, known as dysbiosis, can directly and indirectly contribute to elevated blood cholesterol levels, a primary risk factor for cardiovascular disease (CVD). This review synthesizes current knowledge on the mechanisms by which gut microbiota imbalance leads to hypercholesterolemia, focusing on the modulation of bile acid metabolism, the production of microbial metabolites like trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), and the direct bacterial metabolism of cholesterol. Furthermore, we explore the therapeutic potential of targeting the gut microbiome through dietary interventions, prebiotics, probiotics, and next-generation microbial therapeutics as a strategy for managing cholesterol levels and reducing CVD risk.