Enterococcus faecium WEFA23 from infants lessens high-fat-diet-induced hyperlipidemia via cholesterol 7-alpha-hydroxylase gene by altering the composition of gut microbiota in rats

Abstract

Enterococcus faecium WEFA23 is a potential probiotic strain from Chinese infants with the ability to decrease cholesterol levels. Aiming to explore the mechanism of E. faecium WEFA23 in lowering cholesterol in vivo, we examined the gene transcriptions related to cholesterol metabolism, the composition of bile acids in feces, the synthesis of trimethylamine N-oxide (TMAO) in liver, and the composition of the gut microbiota of rats. We found that E. faecium WEFA23 enhanced the synthesis of bile acids by promoting cholesterol excretion, upregulating the genes transcript level relevant to cholesterol decomposition and transportation, and downregulating the genes involved in cholesterol synthesis. In addition, E. faecium WEFA23 not only downregulated the transcript levels of farnesoid X receptor and fibroblast growth factor 15 as well as flavin-containing monooxygenase 3, but also decreased the TMAO production followed by increasing the CYP7A1 transcript level. Furthermore, when orally administered to rats for 35 d, E. faecium WEFA23 improved the gut microbiota diversity of rats fed a high-fat diet. Therein, the ratio of Bacteroidetes to Firmicutes and the abundance of Rikenellaceae increased, whereas the number of Veillonellaceae decreased. These results suggest that reduction of cholesterol level by E. faecium WEFA23 might be related to the changes in the gut microbiota. Our finding provides important information on lowering cholesterol by E. faecium and reveals that Enterococcus spp. might have the potential to decrease the TMAO level.

Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target

“…Gut colonization with methanogenic archaea reduced plasma TMAO levels and attenuated the burden of AS, with decreased area and fat content in the atherosclerotic plaques, in Apo E −/− mice fed a TMA-supplemented or high choline diet (Ramezani et al, 2018). Enterococcus faecium WEFA23 improved the diversity of the gut microbiota in rats fed a HFD and decreased TMAO production and cholesterol levels (Huang et al, 2018). In human clinical trials, a study of 90 individuals with atherosclerotic CV disease risk factors suggested that Lactofermented Annurca apple puree was an effective functional food that could effectively control plasma TMAO and HDL-C levels (Tenore et al, 2019).…”

The Microbial Metabolite Trimethylamine N-Oxide Links Vascular Dysfunctions and the Autoimmune Disease Rheumatoid Arthritis

“…TMAO downregulates two cytochrome P450 enzymes, cholesterol 7 a-hydroxylase (cyp7A1) that is rate-limiting for bile synthesis, and sterol 27-hydroxylase that participates in diverting cholesterol into bile acids. Hence, it decreases recirculation into the intestine for absorption [70]. Ding et al (2018) showed that TMAO significantly lowers the total bile acid pool size in mice [69].…”

Current Trends of Enterococci in Dairy Products: A Comprehensive Review of Their Multiple Roles

“…Consequently, enterococcal strains that produce this type of antimicrobial peptides are better equipped to establish themselves in the GIT of the host, to directly inhibit pathogens and to modulate the host's gastrointestinal microbiota [230]. The potential for selected enterococci toward modulation of the GIT microbiota in the host, when administered orally, has been demonstrated in animal models [231,232].…”

“…Albano et al [233] demonstrated that an E. lactis strain decreased the cholesterol concentration in broth and as part of a cheese adjunct culture, whereas oral administration of certain E. faecalis or E. faecium strains led to a significant decrease in serum cholesterol levels of hypercholesterolemic animal models [232,234]. In the case of E. faecium, cholesterol excretion was promoted; cholesterol degradation and transportation genes were up-regulated, while genes involved in cholesterol synthesis were down-regulated [234].…”