Insights into the effects of gut microbiota and circulating metabolites on oral cancer: Mendelian randomization analysis and clinical validation.

Background: Prior studies have indicated that alterations in the gut microbiota could potentially influence the occurrence of oral cancer. However, the causal relationship between gut microbiota and oral cancer, as well as whether circulating metabolites serve as mediators, remains unclear. Methods: We employed bidirectional two-sample Mendelian randomization (MR) to explore the causal relationships between gut microbiota, circulating metabolites, and oral cancer. The inverse-variance weighting MR (IVW-MR) and generalized summary data-based MR (GSMR) were used as the primary methods, with various other MR methods used for supplementary analyses. Additionally, we explored the potential mediating effect of circulating metabolites in this relationship. The data on 471 gut microbial taxa, 233 circulating metabolites, and oral cancer used in this study were derived from their respective genome-wide association studies (GWAS). Additional clinical samples were used to validate the Mendelian randomization findings. Results: The IVW-MR and GSMR analyses identified 15 gut microbial taxa positively associated with oral cancer (OR > 1, Conclusions: Oral cancer was found to be causally linked to the gut microbiota, with circulating metabolites acting as mediating factors in this association.