Causal Effects of Gut Microbiota on Oral Cavity Cancer— A Two-Sample Mendelian Randomization Study

Abstract

Abstract Background Recent studies have found that there is a certain correlation between gut microbiota (GM) and oral cavity cancer (OCC). However, their causality is unclear. This study aimed to evaluate the causal relationship between GM and OCC and identify specific pathogenic microbial taxa. Materials and Methods In this Two-Sample Mendelian Randomization Study,GWAS of the microbiome from the MiBioGen consortium (18,340 samples from 24 population-based cohorts) were used as exposure data. In addition, outcome data (357 OCC cases and 372,016 controls) were extracted from the IEU Open GWAS project. To examine the characteristics of potentially pathogenic bacteria in OCC, we performed two-sample Mendelian randomization (MR) analyses-based genome-wide association study (GWAS) summary statistics with the use of inverse-variance-weighting or Wald ratio. Subsequently, sensitivity analyses were performed to explore the robustness of the primary results. Finally, we performed reverse MR analysis to mitigate reverse causality. Result A total of 2,699 single nucleotide polymorphisms (SNPs) associated with 196 bacterial genera were screened as instrumental variables (IVs), and the results suggested that the following taxonomic groups could increase the risk of OCC: order.Burkholderiales, order.Bacillales, class.Betaproteobacteria, genus.Desulfovibrio, order.Pasteurellales, family.Pasteurellaceae, genus.Eubacteriumfissicatenagroup, family.Alcaligenaceae, genus.LachnospiraceaeUCG004, genus.Prevotella7, and genus.Peptococcus.Conversely, genus.Butyrivibrio, genus.Eggerthella, genus.Clostridiumsensustricto1, family.Clostridiaceae1, and phylum.Lentisphaerae exhibited a protective effect against OCC. Conclusion Bacillus orders, Bacillus phylums and Proteobacteria are associated with an increased risk of occ, while Genus Butyrivibrio, genus Eggerthella, and genus Clostridium reduce the risk of OCC development. Our study supports a potential causal relationship between several GM and occ, but how this affects OCC development remains to be further explored.