Figure 19.

GM-dependent FXR-FGF15 signaling improves hepatic presentation in Atg5-deficient mice.Atg5 deficiency in the liver impairs autophagy process and BA homeostasis, which causes liver injury accompanied with cholestasis. Disruption of hepatic BA homeostasis altered the composition of BAs in the intestine and GM , which in turn affects BA composition in the intestine. The changes in intestinal BA composition activate ileal FXR and consequently induce FGF15 expression and reduce BA uptake in the intestine, both of which can improve the homeostasis of enterohepatic BA. Importantly, FGF15 is beneficial to the improvement of the liver injury induced by autophagy deficiency.