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 (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.

Systematic review: human gut dysbiosis induced by non‐antibiotic prescription medications

“…The interactions between statins and bile acids, which share transporters in the intestine, may underlie the interplay between statins and gut microbial composition. Recently, Nolan et al showed in a murine model that Rosuvastatin affected bile acid metabolism and impacted the expression of inflammatory markers known to influence microbial community structure in the gut (i.e., RegIIIy and Camp) . In addition, other side effects of statins such as constipation or laxative effects could potentially arise from gut microbiota alteration.…”

Unraveling Host-Gut Microbiota Dialogue and Its Impact on Cholesterol Levels

“…The first statin, "Mevastatin," which is a metabolic product of Penicillium citrinum, was initially characterized for its antibiotic properties, and statins are now considered as adjuvant antibiotics that can impact antimicrobial resistance (Ko et al, 2017). Consequently, the role of statins deserves to be explored beyond their traditionally established indications in light of their antimicrobial potential as a regulator of gastrointestinal microbiota (Nolan et al, 2017). Only a few studies have shown the impact of the microbiota on statin efficacy.…”

An in vitro evaluation of the effects of different statins on the structure and function of human gut bacterial community

“…term exposures [17]. Statins, the most effective lipid-lowering drugs, which are widely used for the treatment of hypercholesterolemia owing to their inhibition of HMGR protein [36], also have off-target effects including anti-inflammation function [37,38].…”

“…In addition, although the research on the antibacterial activity of FLU has been scarce and more studies are needed [58], it seems that its antifungal activity may be higher than that of other statins [59]. In another study, administration of ROS to mice randomly in the diet for 28 days significantly influenced the structure of the gut microbiota [17]. Some researchers found that ATO and SIM may have a more potent antibacterial activity than ROS, but the clinical strains were less sensitive to statin compared with the standard bacteria [60].…”

“…It has been reported that gut microbiota play roles in the mediation of lovastatin metabolism and consequent pharmacokinetics interactions [15]. The hypolipidemic effects of SIM [16], ROS [17], and ATO [18] were shown to be correlated with the compositions of mice gut microbiota. Statins have certain antibacterial functions and have been described as novel adjuvant antibiotics [10], but we know little about the statin effects on the human gut bacterial microbiota.…”