The influence of rosuvastatin on the gastrointestinal microbiota and host gene expression profiles

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2017-05, Vol.312 (5), p.G488-G497
• Main Authors: Nolan, J A, Skuse, P, Govindarajan, K, Patterson, E, Konstantinidou, N, Casey, P G, MacSharry, J, Shanahan, F, Stanton, C, Hill, C, Cotter, P D, Joyce, S A, Gahan, C G M
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anticholesteremic Agents - administration & dosage; Bacteria; Bile Acids and Salts - biosynthesis; Biosynthesis; Cecum; Cholesterol; Coenzyme A; Community structure; Cyclic AMP; Cytokines - metabolism; Dose-Response Relationship, Drug; Feces; Female; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - physiology; Gastrointestinal tract; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - physiology; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Hydroxymethylglutaryl-CoA reductase; Hypercholesterolemia; Immunologic Factors - metabolism; Inflammation; Intestinal microflora; Metabolism; Mice; Mice, Inbred C57BL; Oral administration; Rodents; Rosuvastatin Calcium - administration & dosage; Statins
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00149.2016

Statins are the most widely prescribed medications worldwide for the treatment of hypercholesterolemia. They inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme 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 on the gut microbiota, host bile acid profiles, and markers of inflammation were analyzed. RSV significantly influenced the microbial community in both the cecum and feces, causing a significant decrease in α-diversity in the cecum and resulting in a reduction of several physiologically relevant bacterial groups. RSV treatment of mice significantly affected bile acid metabolism and impacted expression of inflammatory markers known to influence microbial community structure (including and ) 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 on local gene expression profiles, a finding that should prompt further studies to investigate the implications of statins for gut microbiota stability and health in humans. This work demonstrates that rosuvastatin administration in mice affects the gastrointestinal microbiota, influences bile acid metabolism, and alters transcription of genes encoding factors involved in gut homeostasis and immunity in the gastrointestinal tract.