Enterococcus faecium GEFA01 alleviates hypercholesterolemia by promoting reverse cholesterol transportation via modulating the gut microbiota-SCFA axis
Wenfeng Xu, Kaixiang Zou, Ying Zhan, Yunjie Cai, Zhihong Zhang, Xueying Tao, Liang Qiu, Hua Wei
Abstract
This study aimed to identify cholesterol-lowering commensal strains from healthy lean individuals and to evaluate the cholesterol-lowering capacity of Enterococcus faecium GEFA01 in mice fed a high-cholesterol and high-fat diet. E. faecium GEFA01 was isolated from the feces of a healthy lean individual in a selective basal salt medium supplemented with cholesterol. E. faecium GEFA01 exhibited a cholesterol removal rate (CRR) of 46.13% by coprecipitation, assimilation, and degradation of cholesterol. Moreover, E. faecium GEFA01 significantly decreased the body weight of mice and the levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), hepatic TC, triglycerides (TG), and LDL-C, and increased serum high-density lipoprotein cholesterol (HDL-C) levels in mice fed a high-cholesterol diet compared with the HCD group. We also observed that E. faecium GEFA01 significantly downregulated the gene expression of HMG-CoA reductase ( Hmgcr ), Srebp-1c, Fxr, Shp , and Fgf 15, upregulated the gene expression of low-density lipoprotein receptor ( Ldlr ), Abcg5 / 8, Abca1 , cholesterol 7 alpha-hydroxylase ( Cyp7a1 ), and Lxr in the liver of mice in relative to the HCD group, markedly increased the relative abundance of Lactobacillus, Akkermansia, Bifidobacterium , and Roseburia , and decreased the abundance of Helicobacter in the feces. Collectively, we confirmed that E. faecium GEFA01 exhibited cholesterol-lowering effects in mice fed a high-cholesterol diet, which was achieved through assimilation, coprecipitation, and degradation of cholesterol, and through modulation of the gut microbiota short-chain fatty acid (SCFA) axis that promoted reverse cholesterol transport and bile acid excretion. Our study demonstrated that E. faecium GEFA01 may be used as a probiotic candidate to lower cholesterol levels in the future.