Genetically Predicted Gut Microbiota in Correlation with the Risk of Head and Neck Cancer

Existing evidence supports observational associations between the gut microbiome composition and susceptibility to extraintestinal cancers; however, the causal relationship between gut microbiome composition and the risk of developing head and neck cancer (HNC) remains uncertain. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data to investigate the potential causal link between gut microbiome composition and HNC.

Relevant investigations were conducted to examine the casualties of exposures and outcomes, using inverse variance weighted (IVW), weighted median (WM) and the MR-Egger method. Sensitivity analyses, including the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis, were used to assess pleiotropy and heterogeneity. In addition, the Steiger directionality test was applied to exclude studies with potential directional biases.

Our study identified 16 causal relationships between the genetically predicted abundances of gut microbiota and the risk of developing HNC. After sensitivity analysis on these identified relationships, 10 [class (Actinobacteria, Betaproteobacteria), order Bacillales, family (Ruminococcaceae), genus (Eubacterium_ventriosum_group, Coprococcus2, Coprococcus3, Desulfovibrio, Howardella, Subdoligranulum, Veillonella, Victivallis)] out of the initially identified 16 causal relationships were ultimately validated as being associated with HNC tumors. Steiger directionality test indicated that the MR estimate of causal direction was accurate (All p < 0.05).

Our MR analysis revealed that the gut microbiome composition was causally associated with the risk of developing HNC and could serve as a new biomarker for preventive and therapeutic strategies for HNC.