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<p>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 (<i>n</i> = 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 <i>Bacillota</i>/<i>Bacteroidota</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Manuel Mântua E. Garcia,
  • Virginie Xavier,
  • Ricardo C. Calhelha,
  • Sandrina A. Heleno

摘要

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.