Effect of atorvastatin on the gut microbiota of high fat diet-induced hypercholesterolemic rats

Tariq Jamal Khan,Othman A S Baothman,Mazin A Zamzami,Saleh A Mohamed,Youssri M Ahmed,Muhammad Yasir,Imran Khan,Mohamed G Mehanna

doi:10.1038/s41598-017-19013-2

Tariq Jamal Khan, Othman A S Baothman + Show 6 more

Open Access

https://doi.org/10.1038/s41598-017-19013-2

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Abstract

The aim of the present study was to investigate alterations in gut microbiota associated with hypercholesterolemia and treatment with atorvastatin, a commonly prescribed cholesterol-lowering drug. In this study, seven experimental groups of rats were developed based on diets [high-fat diet (HFD) and normal chow diet (NCD)] and various doses of atorvastatin in HFD and NCD groups. 16S rRNA amplicon sequencing was used to analyze the gut microbiota. Atorvastatin significantly reduced the cholesterol level in treated rats. Bacterial diversity was decreased in the drug-treated NCD group compared to the NCD control, but atorvastatin-treated HFD groups showed a relative increase in biodiversity compared to HFD control group. Atorvastatin promoted the relative abundance of Proteobacteria and reduced the abundance of Firmicutes in drug-treated HFD groups. Among the dominant taxa in the drug-treated HFD groups, Oscillospira, Parabacteroides, Ruminococcus, unclassified CF231, YRC22 (Paraprevotellaceae), and SMB53 (Clostridiaceae) showed reversion in population distribution toward NCD group relative to HFD group. Drug-treated HFD and NCD groups both showed an increased relative abundance of Helicobacter. Overall, bacterial community composition was altered, and diversity of gut microbiota increased with atorvastatin treatment in HFD group. Reversion in relative abundance of specific dominant taxa was observed with drug treatment to HFD rats.

Highlights

Metabolic syndrome has become a global epidemic, and among the associated disorders, hypercholesterolemia is a particular focus of attention because of its cost burden on health care systems worldwide[1]
The GM plays a critical role in the transformation of choline to trimethylamine, which is absorbed by the liver and oxidized by hepatic flavin monooxygenases to produce trimethylamine N-oxide (TMAO), which contributes to cardiovascular diseases (CVDs) development[14,15]
TMAO promotes atherosclerosis, and both TMAO formation and the development of atherosclerosis were suppressed in atherosclerosis-prone mice (C57BL/6 J.Apoe−/−) following antibiotic treatment, which highlights the role of GM in CVD pathogenesis[16,17]

Summary

Introduction

Metabolic syndrome has become a global epidemic, and among the associated disorders, hypercholesterolemia is a particular focus of attention because of its cost burden on health care systems worldwide[1]. A high-fat diet (HFD) has been shown to alter the species composition of intestinal bacteria (i.e., gut microbiota, GM), which in turn play a crucial role in the development of obesity, insulin resistance, and other disorders associated with metabolic syndrome[3,4]. GM-produced SCFAs are associated with increased nutrient uptake and energy harvest via G-protein-coupled receptor activation. They support the development of obesity[6]. Association studies have suggested that GM could affect cholesterol metabolism and interact with cholesterol-lowering drug like pravastatin and simvastatin[7]. Atorvastatin is a commonly used cholesterol-lowering drug to treat hypercholesterolemia. It inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), the enzyme that catalyzes the rate-limiting step of cholesterol synthesis[11]. We sought to discover whether the drug treatment could affect the GM composition and diversity in hypercholesterolemic rats relative to healthy controls

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