Fig. 3: Mechanism of bile acid-induced gastric IM.
From: Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review
Bile acids increase intestinal marker expression via the pathways of FXR/SNAI2/miR-1, FXR/miR-92a-1–5p/FOXD1/NF-κB/CDX2, FXR/SHP/CDX2, FXR/NF-κB/CDX2, TGR5/ERK1/2/HNF4a, miR-21/SOX2/CDX2, and the promoter methylation and downregulation of DKK1 in the stomach. An m6A modification-associated positive feedforward loop between ALKBH5 and NF-kB signaling is involved in generating the IM. Bile acid-induced ALKBH5 enhances ZNF333 levels through an m6A–YTHDF2-dependent manner. In addition, macrophage-derived exosomes facilitate cellular communication between macrophages and gastric epithelial cells in the DCA microenvironment, which promotes the development of SPEM and contributes to gastric IM by transferring miR-30a-5p.
