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. 2019 Nov 27;6:171. doi: 10.3389/fnut.2019.00171

Figure 1.

Figure 1

A number of studies suggest that an increase in microbial BSH activity results in a reduction in stimulation of intestinal FXR. (A) Conjugated bile acids (C-BA) are rapidly absorbed in the terminal ileum but BSH activity reduces the amounts of C-BA locally leading to decreased entry of bile acids (BA) into the cell and reduced engagement of Farnesoid X receptor (FXR). Reduced FXR potentiates the capacity for LXR to become activated and studies show that liver orphan receptor (LXR) activation stimulates the Transintestinal Cholesterol Excretion (TICE) pathway in the gut leading to net cholesterol excretion. (B) Reduced engagement of FXR in the ileum reduces fibroblast growth factor 15 (in mice) or 19 (in humans) (FGF15/19) preventing feedback inhibition of Cyp7A1 and increasing de novo synthesis of bile acids from cholesterol thereby reducing systemic cholesterol levels. (C) Increased excretion of bile acids reduces hepatic signaling to FXR which results in increased potential for activation of LXR and elevated expression of Abcg5/8 allowing for excretion of cholesterol into the bile.