Statins are the most widely prescribed medications worldwide for the treatment of hypercholesterolemia. They inhibit the activity of 3-hydroxy-3-methylglutaryl co enzyme A reductase (HMG-R) an enzyme involved in cholesterol synthesis in higher organisms and in isoprenoid biosynthesis in some bacteria. We hypothesized that statins may influence the microbial community in the gut through either direct inhibition or indirect mechanisms involving alterations to host responses. We therefore examined the impact of rosuvastatin (RSV) on the community structure of the murine gastrointestinal microbiota. RSV was orally administered to mice and the effects upon the gut microbiota, host bile acid profiles and markers of inflammation were analysed. RSV significantly influenced the microbial community in both the caecum and faeces, causing a significant decrease in alpha diversity in the caecum and resulting in a reduction of several physiologically relevant bacterial groups. RSV treatment of mice significantly affected bile acid metabolism and impacted upon expression of inflammatory markers known to influence microbial community structure (including RegIIIγ and Camp) in the gut. This study suggests that a commonly used statin (RSV) leads to an altered gut microbial composition in normal mice with attendant impacts upon local gene expression profiles, a finding which should prompt further studies to investigate the implications of statins for gut microbiota stability and health in humans.
- bile acid
- Copyright © 2016, American Journal of Physiology-Gastrointestinal and Liver Physiology