Cholesterol conversion in the human gut microbiome

Florian Fricke is Professor at the Deptartment of Microbiome & Applied Bioinformatics, Institute for Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany.

Excess blood cholesterol is a risk factor for cardiovascular disease, with clinical interventions aiming to reduce cholesterol uptake from exogenous, dietary sources or inhibiting endogenous cholesterol biosynthesis. Cholesterol metabolism also involves the gastrointestinal microbiota, which has been shown to convert cholesterol to non-absorbable coprostanol. However, the physiological and clinical relevance of gut microbiota-mediated cholesterol conversion remain largely unknown.

To study microbiota contributions to human cholesterol metabolism under varying conditions, we determined fecal microbiota and lipid profiles, and serum lipid biomarkers, in two independent human cohorts, including healthy individuals following a 6-week ketogenic diet (KETO study) and obese individuals randomly assigned to a 2-year normocaloric diet of either high or low-fat and variable (cellular/acellular) carbohydrate quality (CARBFUNC study).

Individuals could be assigned to distinct high and low-cholesterol converter types, based on fecal coprostanol-to-cholesterol ratio. Interestingly, high and low-cholesterol converters contributed comparable fractions to the healthy KETO and obese CARBFUNC cohorts before the interventions. Cholesterol converter type was associated with fecal microbiota composition across both cohorts, but not serum lipid levels (total cholesterol, triglycerides, HDL, and LDL). Transition to a high-fat diet consistently increased cholesterol conversion in previous low-converters, whereas transition to the low-fat, high-quality carbohydrate diet decreased cholesterol conversion in previous high-converters from the CARBFUNC cohort. Independently of the cholesterol converter type, low-fat diets improved cardiovascular risk markers (reduced total cholesterol and LDL).

In summary, we show that fecal cholesterol conversion is a functionally and structurally relevant feature of the human fecal microbiome. Although influenced by diet, high and low-cholesterol converter types were equally abundant among healthy and obese individuals. Serum lipid biomarkers for cardiovascular risk were not linked to intestinal cholesterol conversion but rather appear to be influenced by diet composition and quality.

Moderator: Simon Dankel

Lenke til streaming: https://uib.zoom.us/j/66246632734?pwd=REZFS1pVdERGVCtSTmFQZTc4UlUxdz09