Investigating the causal role of the gut microbiota in esophageal cancer and its subtypes: a two-sample Mendelian randomization study

Abstract Background Through research on the gut microbiota (GM), increasing evidence has indicated that the GM is associated with esophageal cancer (ESCA). However, the specific cause-and-effect relationship remains unclear. In this study, Mendelian randomization (MR) analysis was applied to investigate the causal relationship between the GM and ESCA, including its subtypes. Methods We collected information on 211 GMs and acquired data on ESCA and its subtypes through genome-wide association studies (GWASs). The causal relationship was primarily assessed using the inverse variance weighted (IVW) method. Additionally, we applied the weighted median estimator (WME) method, MR–Egger method, weighted mode, and simple mode to provide further assistance. Subsequent to these analyses, sensitivity analysis was conducted using the MR–Egger intercept test, MR-PRESSO global test, and leave-one-out method. Result Following our assessment using five methods and sensitivity analysis, we identified seven GMs with potential causal relationships with ESCA and its subtypes. At the genus level, Veillonella and Coprobacter were positively correlated with ESCA, whereas Prevotella9 , Eubacterium oxidoreducens group , and Turicibacter were negatively correlated with ESCA. In the case of esophageal adenocarcinoma (EAC), Flavonifractor exhibited a positive correlation, while Actinomyces exhibited a negative correlation. Conclusion Our study revealed the potential causal relationship between GM and ESCA and its subtypes, offering novel insights for the advancement of ESCA diagnosis and treatment.