Causal association between oral microbiota and hepatocellular carcinoma in East Asian populations: a Mendelian randomization study.

OBJECTIVES

Emerging evidence highlights the crucial role of the oral microbiota in various malignancies, but its causal relationship with hepatocellular carcinoma (HCC) remains largely unexplored. This study aimed to investigate the causal association between oral microbiota composition and HCC risk in East Asian populations using Mendelian randomization (MR) analysis.

METHODS

We performed a two-sample Mendelian randomization to investigate the causal association of 309 tongue dorsum microbiomes and 285 salivary microbiomes with liver cancer progression using the latest pooled data from genome-wide association study (GWAS) of oral microbiomes in East Asian populations. We selected single nucleotide polymorphism (SNP) independent of confounders as the instrumental variable (IV) for causal inference analysis using various Mendelian randomization statistical techniques. The heterogeneity and pleiotropy of the IV was evaluated to ensure the reliability of the results.

RESULTS

Our analysis revealed a complex association between specific bacterial genera in the oral microbiome and liver cancer. Streptococcus showed a mixed association with hepatocellular carcinoma, while Oribacterium and Centipeda showed a positive correlation with HCC occurrence. Gemella genus was negatively correlated with HCC. Heterogeneity or pleiotropy of the IV was not detected in the sensitivity analysis.

CONCLUSIONS

This study provides the first Mendelian randomization evidence linking oral microbiota to HCC susceptibility in East Asian populations. Our findings suggest causal roles of specific oral bacterial taxa in hepatocarcinogenesis, and offer new insights into the mechanisms of the oral-liver axis and potential microbial targets for HCC prevention and treatment.