Abstract: The purpose of this study was to investigate the alleviating effect of Akkermansia muciniphila ONE (AKK ONE) on high-cholesterol diet-induced hypercholesterolemia in mice. Four-week gavage of AKK ONE was found to improve blood lipid levels in hypercholesterolemic mice. Specifically, it significantly reduced the contents of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in serum and liver, increased the content of high-density lipoprotein cholesterol (HDL-C), alleviated liver damage, reduced the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA), and improved fasting blood glucose levels and glucose tolerance. Further analysis of intestinal flora and metabolites showed that AKK ONE significantly increased the abundance of Faecalibaculum, Oscillospira, Bacteroides and Akkermansia in the intestine of mice, increased the contents of short-chain fatty acids (SCFAs) including acetic acid, isobutyric acid and valeric acid, and regulated the composition of intestinal bile acids (BAs) especially secondary BAs. In summary, AKK ONE improved high cholesterol diet-induced hypercholesterolemia by regulating the abundance of intestinal flora, especially increasing the abundance of SCFAs-producing bacteria, thereby increasing the contents of fecal SCFAs and enhancing the transformation of cholesterol into BAs. This study provides a new insight into the relationship between next-generation probiotics and intestinal flora and metabolites, which will serve as the basis for the potential application of AKK ONE in alleviating hypercholesterolemia.

Key words: Akkermansia muciniphila ONE; hypercholesterolemia; intestinal flora; short-chain fatty acid; bile acid