Stool samples from individuals in the Framingham Heart Study cohort
Efforts to investigate how gut microbes influence human metabolism are critical to understand how this microbial community impacts human health and disease. For example, while the metabolism of cholesterol to the poorly absorbed sterol coprostanol by the human gut microbiota is hypothesized to play a role in modulating human serum cholesterol concentrations, there is a gap in knowledge regarding which enzymes and microbes are responsible for this metabolism in the human gut. Here we identify a novel group of cholesterol oxidoreductase enzymes in the gut that are involved in the metabolism of cholesterol to cholestenone, an on-pathway intermediate to the final product coprostanol. These enzymes are prevalent in geographically diverse gut microbiota and are encoded by a clade of uncultured microorganisms. Individuals with coprostanol-forming microbes have significantly lower concentrations of fecal cholesterol and lower concentrations of serum total cholesterol (-0.14 mmol/L in TC; 95% CI: -0.27, -0.02) and triglycerides. Thus, the metabolism of cholesterol by an uncultured clade of microorganisms may play an important role in modulating both intestinal and serum cholesterol concentrations, directly impacting human health.