Microbial Conversion of Cholesterol to Coprostanol

Cholesterol is a component in all mammalian cellular membranes and a precursor of steroid hormones, vitamin D, and bile acids. Pathophysiologically, it is thought to be an important factor in the pathogenesis of atheromatous arterial disease, hypertension, cancer of the large bowel, and other disorders (8). The intestinal cholesterol is derived mainly from two sources—partly from synthesis occurring in the liver and the small intestine and partly from foods of animal origin. The main elimination routes for the plasma cholesterol are biliary excretion of cholesterol into the intestine as well as hepatic conversion of cholesterol to bile acids. The intestinal cholesterol can be absorbed to the entero-hepatic circulation or undergo microbial conversion. The major microbial metabolite is (unabsorbable) coprostanol which is excreted with the feces. The organisms responsible for the conversion are all strictly anaerobic, Gram-positive, nonspore-forming coccoid rods, probably belonging to the genus Eubacterium.

By definition, any germ-free organism lacks the intestinal microbial excretion route for cholesterol. From a functional point of view, conversion of cholesterol to coprostanol can be looked upon as a sharp "microbial intestinal knife," influencing the normal entero-hepatic circulation of cholesterol (26). As early as 1959, higher serum cholesterol concentrations were found in germ-free than in conventional rats fed the same diet (27).

Studies in many mammalian species show that this function is present in all animals soon after birth (5). However, data from infants indicate that this function is established—when established—in the second part of their first year. Comparative data from several countries show that one of five healthy adults might be a "non-excretor" or "low-excretor" of coprostanol. We have hypothesized that a genetically determined receptor determines whether an environmental receptor modulation determines if a cholesterol converting microbiota will be established. So far, however, the nature of the(se) receptor(s) is still unknown (8).

It has been claimed by some probiotic-producing companies that their microbial products decrease the level of plasma cholesterol, by mechanisms(s) still under discussion. Gnotobiotic animal studies seem very applicable for further mechanistic investigations.

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Blood Pressure Health

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