| Summary: | Hypercholesterolemia can cause many diseases, but it can effectively regulated by <i>Lactobacillus</i>. This study aimed to evaluate the cholesterol-lowering mechanism of <i>Enterococcus faecium</i> strain 132 and <i>Lactobacillus</i><i>paracasei</i> strain 201. These results showed that both the strains decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), liver TC and TG and increased fecal TC, TG and total bile acid (TBA) levels. Additionally, both strains also reduced glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST) and levels of tissue inflammation levels to improve the lipid profile, and they reduced fat accumulation partially by alleviating inflammatory responses. Furthermore, both strains regulated the expression of the <i>CYP8B1</i>, <i>CYP7A1, SREBP-1</i>, <i>SCD1</i> and <i>LDL-R</i> gene to promote cholesterol metabolism and reduce TG accumulation. Interventions with both strains also altered the gut microbiota, and decreasing the abundance of Veillonellaceae, Erysipelotrichaceae and <i>Prevotella</i>. Furthermore, fecal acetic acid and propionic acid were increased by this intervention. Overall, the results suggested that <i>E. faecium</i> strain 132 and <i>L. paracasei</i> strain 201 can alleviate hypercholesterolemia in rats and might be applied as a new type of hypercholesterolemia agent in functional foods.
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