ASCVD
In this study, we aimed to explore the bioactive molecules derived from Bacteroidota, the dominant gut microbiota phylum, which is known to be crucial for human health but remains largely unexplored in the context of atherosclerosis. We developed an in vitro screening pipeline based on LDL uptake assays to identify these molecules. Among the identified compounds, one compound emerged as the most potent, demonstrating anti-atherosclerotic effects in a mouse model. Mechanistically, this compound directly inhibits hepatic HMGCR, a key enzyme in cholesterol synthesis, thereby enhancing plasma LDL-C clearance. Our findings highlight the therapeutic potential of Bacteroidota-derived compound in promoting cholesterol homeostasis and managing atherosclerotic cardiovascular disease (ASCVD).