Gut Microbiota-Derived Small Molecules in Atherosclerosis: Biosynthesis, Mechanistic Insights, and Translational Potential

Atherosclerosis (AS) is the pathological foundation of most cardiovascular diseases and remains a major cause of global mortality. Increasing evidence implicates gut microbiota-derived small molecules (GMDSMs) as critical chemical modulators of lipid metabolism, vascular inflammation, and thrombosis. In this review, we summarize representative GMDSMs that have been mechanistically linked to AS, including amino acid derivatives, fatty acids, trimethylamine N -oxide, bile acids, and bacterial cell membrane compartments. For each class, we highlight representative biosynthetic enzymes, microbial taxa, and host targets that mediate atherogenic or protective effects. Mechanistic studies have established distinct microbial–host cometabolic pathways linking diet, microbiota composition, and cardiovascular outcomes. We further discuss emerging therapeutic strategies that modulate microbial metabolism or harness beneficial metabolites for AS prevention. Elucidating the biosynthetic diversity and functional logic of these molecules will accelerate the development of microbiome-based diagnostics and interventions for cardiovascular disease.