Abstract
BACKGROUND: Growing evidence suggests that there is a link between the oral microbiota and the development of digestive system cancers (DSCs). Nonetheless, the causal relationship between the oral microbiota and DSCs has yet to be established. METHODS: To evaluate the causal relationship between oral microbiota and DSCs, we employed Genome-wide association study (GWAS) summary statistics for both oral microbiota and DSCs, in conjunction with bidirectional two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms, which were free from confounding factors, were used as instrumental variables to infer causation. Sensitivity analyses were conducted to assess the robustness of our findings. This study employed datasets encompassing a wide range of cancer cases and controls, with an emphasis on Asian populations. RESULTS: Our analysis of 116 oral microbiota (65 from tongue dorsum and 51 from saliva) uncovered intricate causal associations with seven types of DSCs. We discovered that the genus TM7x (OR > 1, adjusted p < 0.05) poses a risk for hepatic bile duct cancer, and the genus Leptotrichia (OR = 6.38, 95%CI = 1.84-22.10, adjusted p < 0.05) poses a risk for pancreatic cancer. Furthermore, reverse MR analysis showed that DSCs influence the relative abundance of certain oral microbiota strains. CONCLUSION: Our MR analysis has confirmed that there is a causal association between the oral microbiota and DSCs. This finding offers potential for creating novel microbial markers and treatments that modify the microbiota specifically for DSC patients.