Cholesterol-to-Coprostanol Conversion by the Gut Microbiota: What We Know, Suspect, and Ignore

Abstract

Every day, up to 1 g of cholesterol, composed of the unabsorbed dietary cholesterol, the biliary cholesterol secretion, and cholesterol of cells sloughed from the intestinal epithelium, enters the colon. All cholesterol arriving in the large intestine can be metabolized by the colonic bacteria. Cholesterol is mainly converted into coprostanol, a non-absorbable sterol that is excreted in the feces. Interestingly, cholesterol-to-coprostanol conversion in human populations is variable, with a majority of high converters and a minority of low or inefficient converters. Two major pathways have been proposed, one involving the direct stereospecific reduction of the Δ5 double bond direct while the indirect pathway involves the intermediate formation of 4-cholelesten-3-one and coprostanone. Despite the fact that intestinal cholesterol conversion was discovered more than a century ago, only a few cholesterol-to-coprostanol-converting bacterial strains have been isolated and characterized. Moreover, the responsible genes were mainly unknown until recently. Interestingly, cholesterol-to-coprostanol conversion is highly regulated by the diet. Finally, this gut bacterial metabolism has been linked to health and disease, and recent evidence suggests it could contribute to lower blood cholesterol and cardiovascular risks.

Keywords: bile acids; cholesterol; coprostanol; feces; gut microbiome; intestine.

Figure 1

Estimation of daily cholesterol input and output in the healthy adult.

Figure 2

Planar representation of cholesterol (A) and coprostanol (B).

Figure 3

Direct and indirect pathways for the conversion of cholesterol to coprostanol by the gut microbiota. The indirect pathway (II, large grey arrow) is by far the most probable as evidenced by identification of the intermediates in crude feces and cultures of pure active strains. The direct pathway (I) cannot be excluded but never received any proof of evidence. Note that isomerization of cholesterol to allocholesterol and then reduction of allocholesterol to coprostanol (pathway III) are chemical reactions that, until proved otherwise, do not proceed in any organism. * Intermediate seen in GC-MS analyses of feces or pure active cultures. Micro-organisms and enzymes involved in the considered reaction are mentioned; black and grey characters correspond to confirmed and uncertain knowledge, respectively. A micro-organism is confirmed if it has been shown to process to the reaction in pure culture. An enzyme is confirmed if it has been purified and characterized in at least one gut micro-organism.