Hypocholesterolemic agents and the gut microbiota: a review of interactions and modulatory activity

Hypercholesterolemia is a major risk factor that contributes to the development and/or aggravation of cardiovascular diseases. High cholesterol levels are frequently managed with hypocholesterolemic agents, either synthetic or natural. Beyond their cholesterol-lowering effects, these compounds can also affect the host's gut microbiota. This review examined the extent and quality of the modulatory activity of selected hypocholesterolemic agents (n = 11) on the gut microbiota profile, based on a comprehensive literature search and analysis of interactions between the gut microbiota and distinct cholesterol-lowering compounds. With a few exceptions, anti-cholesterol interventions were associated with changes in gut microbiota β-diversity and a decrease in the Bacillota/Bacteroidota ratio. Further analyses at family and genus levels revealed patterns of modulation that clustered by molecular target and bioavailability. Overall, gut microbiota shifts favoured short-chain fatty acid (SCFA)-producing bacteria over inflammation-promoting taxa. Furthermore, for some anti-cholesterol compounds, microbial metabolism and the concomitant release of bioactive metabolites suggested partially microbiota-dependent cholesterol-lowering effects. These findings may inform new strategies for cholesterol management from a gut-health perspective; however, further research is needed to establish causality and draw robust conclusions regarding medication-microbiota relationships.