Sulfonation metabolism in the gut microbiota is the main metabolic pathway of cholesterol in hypercholesterolemic mice

Abstract

The interactions between dietary cholesterol and intestinal microbiota strongly affect host health. Sulfonation is a major conjugating pathway responsible for regulating the chemical and functional homeostasis of endogenous and exogenous molecules. However, the role of cholesterol sulfonation metabolism in the host remains unclear. This work was designed to profile cholesterol-specific host–microbe interaction and conversion focusing on cholesterol sulfonation metabolism. Results indicated that the serum and fecal cholesterol sulfate (CHS) levels were significantly higher than those of total bile acid (TBA) levels in hypercholesterolemic mice. Deletion of the gut microbiota by antibiotics could dramatically increase total cholesterol (TC) levels but it decreased CHS levels in a pseudo-germ-free (PGF) mouse host. 16S rRNA gene sequencing assay and correlation analysis between the abundance of various intestinal bacteria (phylum and class) and the CHS/TC ratio showed that the intestinal genera Bacteroides contributed essentially to cholesterol sulfonation metabolism. These results were further confirmed in an in situ and ex vivo mouse intestinal model, which indicated that the sulfonation metabolism rate of cholesterol could reach 42% under high cholesterol conditions. These findings provided new evidence that the sulfonation metabolic pathway dominated cholesterol metabolism in hypercholesterolemic mice and microbial conversion of cholesterol-to-CHS was of vital importance for cholesterol-lowering by Bacteroides. This suggested that the gut microbiota could regulate cholesterol metabolism and that it was feasible to reduce cholesterol levels by dietary interventions involving the gut microbiota.