Bacteria Influence Cholesterol Conversion

Like the discoveries with genomics, microbiomics has already proven to be incredibly productive and many of those discoveries have been noted in this blog.

In this new paper Swedish researcher report that bacteria play a role in cholesterol metabolism. They find that gut bacteria produce FXR antagonists which eventually leads to reduced clearance of bile acids by the liver. 

From Cell Metabolism, Volume 17, Issue 2, 155-156, 5 February 2013

http://www.cell.com/cell-metabolism/abstract/S1550-4131(13)00011-9

Gut Microbiota Regulates Bile Acid Metabolism by Reducing the Levels of Tauro-beta-muricholic Acid, a Naturally Occurring FXR Antagonist

Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver. Here we profiled the bile acid composition throughout the enterohepatic system in germ-free (GF) and conventionally raised (CONV-R) mice. We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice. Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7α-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms. Importantly, we identified tauro-conjugated beta- and alpha-muricholic acids as FXR antagonists. These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum.

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