AUTHOR=Xu Wenfeng , Zou Kaixiang , Zhan Ying , Cai Yunjie , Zhang Zhihong , Tao Xueying , Qiu Liang , Wei Hua 

TITLE=Enterococcus faecium GEFA01 alleviates hypercholesterolemia by promoting reverse cholesterol transportation via modulating the gut microbiota-SCFA axis

JOURNAL=Frontiers in Nutrition

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1020734

DOI=10.3389/fnut.2022.1020734

ISSN=2296-861X

ABSTRACT=<p>This study aimed to identify cholesterol-lowering commensal strains from healthy lean individuals and to evaluate the cholesterol-lowering capacity of <italic>Enterococcus faecium</italic> GEFA01 in mice fed a high-cholesterol and high-fat diet. <italic>E. faecium</italic> GEFA01 was isolated from the feces of a healthy lean individual in a selective basal salt medium supplemented with cholesterol. <italic>E. faecium</italic> GEFA01 exhibited a cholesterol removal rate (CRR) of 46.13% by coprecipitation, assimilation, and degradation of cholesterol. Moreover, <italic>E. faecium</italic> 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 <italic>E. faecium</italic> GEFA01 significantly downregulated the gene expression of HMG-CoA reductase (<italic>Hmgcr</italic>), <italic>Srebp-1c, Fxr, Shp</italic>, and <italic>Fgf</italic> 15, upregulated the gene expression of low-density lipoprotein receptor (<italic>Ldlr</italic>), <italic>Abcg5</italic>/<italic>8, Abca1</italic>, cholesterol 7 alpha-hydroxylase (<italic>Cyp7a1</italic>), and <italic>Lxr</italic> in the liver of mice in relative to the HCD group, markedly increased the relative abundance of <italic>Lactobacillus, Akkermansia, Bifidobacterium</italic>, and <italic>Roseburia</italic>, and decreased the abundance of <italic>Helicobacter</italic> in the feces. Collectively, we confirmed that <italic>E. faecium</italic> 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 <italic>E. faecium</italic> GEFA01 may be used as a probiotic candidate to lower cholesterol levels in the future.</p>