Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Therefore, the mechanism of IM has been the focus of basic and clinical research. Helicobacter pylori (H. pylori) infection has been recognized as the main pathogenesis of gastric IM. However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. In addition, microRNAs, exosomes, and epigenetics are also involved in the occurrence and development of bile acid-induced gastric IM. Currently, the relevant research is still very few. The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. This article mainly reviews the physiology and pathology of bile acid, mechanism of gastric IM induced by bile acid, bile acid receptors, and so on, in order to provide reference for further research.

Tumor immune microenvironment (TIME), a tumor-derived immune component, is proven to be closely related to the development, metastasis, and recurrence of tumors. Gut microbiota and its fermented-metabolites short-chain fatty acids (SCFAs) play a critical role in maintaining the immune homeostasis of gastrointestinal tumors. Consisting mainly of acetate, propionate, and butyrate, SCFAs can interact with G protein-coupled receptors 43 of T helper 1 cell or restrain histone deacetylases (HDACs) of cytotoxic T lymphocytes to exert immunotherapy effects. Studies have shed light on SCFAs can mediate the differentiation and function of regulatory T cells, as well as cytokine production in TIME. Additionally, SCFAs can alter epigenetic modification of CD8+ T cells by inhibiting HDACs to participate in the immune response process. In gastrointestinal tumors, the abundance of SCFAs and their producing bacteria is significantly reduced. Direct supplementation of dietary fiber and probiotics, or fecal microbiota transplantation to change the structure of gut microbiota can both increase the level of SCFAs and inhibit tumor development. The mechanism by which SCFAs modulate the progression of gastrointestinal tumors has been elucidated in this review, aiming to provide prospects for the development of novel immunotherapeutic strategies.