Molecular characterization of gut microbiota in high-lipid diet-induced hyperlipidemic rats treated with simvastatin

Hyperlipidemia is a major risk factor for cardiovascular diseases. Simvastatin (SV), a cholesterol-lowering agent, has been widely used in the treatment of hyperlipidemia. Gut microbiota is known to influence drug response, including that to statins. However, the effect of SV on the gut microbiota of hyperlipidemic rats is not fully understood. To investigate the influence of SV on gut microbiota in hyperlipidemic rats, the molecular characterization of gut microbiota and the potential functions of genes involved in the downstream metabolic pathways were analyzed using high-throughput sequencing technology and the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States approach. The results revealed that SV treatment could reduce the gut microbial diversity and drive marked remodeling of the fecal bacterial community composition. At the phylum level, the relative abundance of Firmicutes and Actinobacteria was decreased following SV therapy, whereas that of Bacteroidetes was elevated. At the genus level, the percentage of the genera Bacteroides, Sutterella and Phascolarctobacterium was significantly increased, but that of Bifidobacterium, Ruminococcaceae_NK4A214, Ruminococcaceae_UCG-009, Intestinimonas and Tyzzerella was significantly decreased. Additionally, functional prediction analysis indicated that in the SV-associated microbiota, genes involved in energy, carbohydrate, amino acid and nucleotide metabolism likely exhibited enrichment. Briefly, to the best of our knowledge, the present study was the first to establish a profound and comprehensive association between the SV-induced alterations of the gut flora and the consequent influences of downstream metabolic pathways by gut microbiota. These findings suggested that the gut microbiota may contribute to the SV hypolipidemic efficacy in the progression of hyperlipidemia, which could provide insights for the prevention and treatment of hyperlipidemia.