Fig. 1

The mechanism of gut microbiota in carcinogenesis. A). Chronic inflammation: Inflammation accelerates the invasion, metastasis, and progression of the tumor. Inflammatory cytokines are directly involved in DNA damage and lead to inflammation-associated cancer. Inflammatory factors can inhibit tumor suppressor genes such as p53, and activate oncogenes such as KRAS. Colibactin produced by Escherichia coli and Klebsiella pneumoniae can cause DNA damage and mutations and trigger chronic inflammation. Proliferation of Proteobacteria is associated with an increase in IL-6 and IL-8. Polysaccharide A (PSA) expressed by symbiont Bacteroides fragilis can suppress IL-17 induced by Helicobacter hepaticus. Specific filamentous bacteria (SFB) are involved in the production of IL-17 and the regulation of gut immune maturation. B). Immune regulation: Dysbiosis of the gut microbiota is associated with cellular immunity and immune function, which affects GC development. The innate immune system can detect the structural components of gut microbiota such as flagellin, lipopolysaccharide (LPS), and peptidoglycans through Toll-like receptors (TLRs) and NOD-like receptors and regulate the innate immune response. C). Microbial metabolites: Butyrate through interaction with G protein-coupled receptor 43 (GPR43), up-regulating IL10 expression, and activating histone deacetylase inhibition (HDACi) can induce the differentiation of IL10-producing T cells and regulatory T cells. The Lipoteichoic acid (LTA) produced by the gut microbiota specifically binds to CD14 (cluster of differentiation 14) or TLR2 and causes the excessive secretion of proinflammatory agents, thus promotes malignant transformation. LPS produced by intestinal microbiota enhances tumor development by regulating the high expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and activating the epidermal growth factor receptor (EGFR) signaling pathway