Association of Gut Microbiota and Gastric Cancer: a Two-sample Mendelian Randomization Study

Abstract

Abstract Purpose Numerous observational studies and clinical trials have presented evidence of a correlation between gut microbiota and multiple cancers. However, the precise causal relationship between gut microbiota and gastric cancer remains unclear. The objective of this study was to delve into the causal role of gut microbiota in the development of gastric cancer. Methods To assess the causal relationship between gut microbiota and gastric cancer, a two-sample Mendelian randomization study was conducted. This study utilized genome-wide association study (GWAS) summary statistics from the MiBioGen and IEU Open GWAS projects. Several statistical approaches, including inverse variance weighted, simple mode, MR-Egger, weighted median, weighted model, and MR-PRESSO, were employed to investigate the causal relationship between gut microbiota and gastric cancer. Additionally, we performed a reverse Mendelian randomization analysis of the gut microbiota that was found to have a causal association with gastric cancer. Results Through Mendelian randomization analysis, a causal relationship between gut microbiota dysbiosis and the risk of gastric cancer was identified. Specifically, six groups of gut microorganisms, including short-chain fatty acid (SCFAs)-producing bacteria, demonstrated a protective effect against gastric cancer. Conversely, four groups of gut microorganisms, including the genus. Clostridium sensu stricto1, exhibited a promotive effect on gastric cancer. No inverse causal effect of gastric cancer on the distribution of intestinal microbiota was observed. Furthermore, no significant heterogeneity or horizontal pleiotropy of instrumental variables was detected. Conclusion The findings of this study indicate that The imbalance of gut mocrobiota, especially the reduction of SCFAs-producing bacteria, may promote the occurrence of gastric cancer Consequently, this study serves as an essential reference for future research pertaining to gut microbiota-mediated cancer.