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. 2022 Oct 27;13:1003376. doi: 10.3389/fimmu.2022.1003376

Figure 2.

Figure 2

The role of gut microbiota in BAs related negative and positive regulation pathways of liver regeneration. FGF19 inhibit the rate-limiting enzyme for the synthesis of BAs, CYP7a1 and thus down-regulate BAs synthesis. And there is a positive feedback regulation of FGF19 by acting on FGFR on hepatocytes. BAs released into the intestine by the gallbladder act on FXR on intestinal epithelial cells and induce the release of FGF19 and FGF19. Then FGF19 reach liver through portal vein and function in the same way. FGF15 bond with FGFR4 to increase SHP1 expression in hepatocytes and decrease the level of CYP7a1 and CYP8b1. Secondary BAs converted from primary BAs by gut microbiota can inhibit FXR and activate TGR5, secreting inflammatory cytokines. These cytokines can be collected by portal vein and function to delay liver regeneration. The activation of TGR5 can also increase the bile secretion and mobility to reduce BAs overload in liver.