The influence of , proton pump inhibitor, and obesity on the gastric microbiome in relation to gastric cancer development.

infection is still the main risk factor for the development of gastric cancer (GC). We explore the scientific evidence for the role of the gastric microbiome beyond () in gastric carcinogenesis. The composition of the gastric microbiome in healthy individuals, in presence and absence of infection, in proton pump inhibitor (PPI)-users, obese individuals, and GC patients was investigated. Possible mechanisms for microbial involvement, limitations of available research and options for future studies are provided. A common finding amongst studies was increased levels of , , , and in healthy individuals or those with negative gastritis In PPI-users the risk for GC increases with the treatment duration, and the gastric microbiome shifts, with the most consistent increase in the genus . Similarly, in obese individuals, was the most abundant genus, with an increased risk for cardia GC. The genera and were found to be more prominent in GC patients in multiple studies. Potential mechanisms of non- microbiota contributing to GC are linked to lipopolysaccharide production, contribution to inflammatory pathways, and the formation of N-nitroso compounds and reactive oxygen species. In conclusion, the knowledge of the gastric microbiome in GC is mainly descriptive and based on sequencing of gastric mucosal samples. For a better mechanistic understanding of microbes in GC development, longitudinal cohorts including precancerous lesions, different regions in the stomach, and subtypes of GC, and gastric organoid models for diffuse and intestinal type GC should be employed.