The interplay of the microbiome, host genetics, and epigenetic modifications in gastric cancer.

Gastric cancer is one of the most prevalent gastrointestinal malignancies worldwide, with Helicobacter pylori infection, host genetic susceptibility and environmental exposure serving as major driving risk factors. Accumulating studies have demonstrated that host genetics, the microbiome and epigenetic modifications collectively govern gastric cancer initiation and progression. These three components form a bidirectional regulatory axis: host genetic profiles and epigenetic remodeling shape the composition of endogenous microbial communities, while the microbiome and its metabolites trigger epigenetic reprogramming to modulate transcription of oncogenes and tumor suppressors. Deciphering this intricate tripartite regulatory network holds great potential to facilitate the development of precise therapeutic interventions for gastric cancer. This review delineates the respective roles of host genetics, the microbiome and epigenetic modifications throughout gastric cancer evolution and summarizes corresponding prospective intervention strategies. We elaborate on the reciprocal interplay between the microbiome and host genetic/epigenetic factors, and highlight the vital clinical significance of this crosstalk for gastric cancer prevention and treatment.