title: The influence of rosuvastatin on the gastrointestinal microbiota and host gene expression profiles.
abstract: 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 (includingRegIIIγandCamp) 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.NEW & NOTEWORTHYThis 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.
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: J A
authors.initials: JA
authors.lastname: Nolan
authors.affiliation: Teagasc Food Research Centre, Biosciences Department, Moorepark, Fermoy, Cork, Ireland.
authors.forename: P
authors.initials: P
authors.lastname: Skuse
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: K
authors.initials: K
authors.lastname: Govindarajan
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|School of Microbiology, University College Cork, Cork, Ireland.|Teagasc Food Research Centre, Biosciences Department, Moorepark, Fermoy, Cork, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Patterson
authors.affiliation: School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: N
authors.initials: N
authors.lastname: Konstantinidou
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: P G
authors.initials: PG
authors.lastname: Casey
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|School of Microbiology, University College Cork, Cork, Ireland.|School of Medicine, University College Cork, Cork, Ireland; and.
authors.forename: J
authors.initials: J
authors.lastname: MacSharry
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: F
authors.initials: F
authors.lastname: Shanahan
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|Teagasc Food Research Centre, Biosciences Department, Moorepark, Fermoy, Cork, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: Stanton
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: Hill
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|Teagasc Food Research Centre, Biosciences Department, Moorepark, Fermoy, Cork, Ireland.
authors.forename: P D
authors.initials: PD
authors.lastname: Cotter
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|School of Microbiology, University College Cork, Cork, Ireland.|School of Medicine, University College Cork, Cork, Ireland; and.
authors.forename: S A
authors.initials: SA
authors.lastname: Joyce
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland; c.gahan@ucc.ie.|School of Microbiology, University College Cork, Cork, Ireland.|School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: C G M
authors.initials: CGM
authors.lastname: Gahan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D001647:Bile Acids and Salts / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007155:Immunologic Factors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage*
chemical_list: D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D016207:Cytokines; D007155:Immunologic Factors; D000068718:Rosuvastatin Calcium
keywords: bile acid; inflammation; isoprenoid; microbiota; statin