A Mendelian randomization analysis reveals the multifaceted role of the skin microbiota in liver cancer.

ABSTRACT

Background: Hepatocellular carcinoma (HCC, or hepatic cancer, HC) and cholangiocarcinoma (CCA, or hepatic bile duct cancer, HBDC) are two major types of primary liver cancer (PLC). Previous studies have suggested that microbiota can either act as risk factors or preventive factors in PLC. However, no study has reported the relationship between skin microbiota and PLC. Therefore, we conducted a two-sample Mendelian randomization (MR) study to assess the causality between skin microbiota and PLC. Methods: Data from the genome-wide association study (GWAS) on skin microbiota were collected. The GWAS summary data of GCST90018803 (HBDC) and GCST90018858 (HC) were utilized in the discovery and verification phases, respectively. The inverse variance weighted (IVW) method was utilized as the principal method in our MR study. The MR-Egger intercept test, Cochran's Q-test, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis were conducted to identify the heterogeneity and pleiotropy. Results: The results showed that Veillonella (unc.) plays a protective role in HBDC, while the family Neisseriaceae has a positive association with HBDC risk. The class Betaproteobacteria, Veillonella (unc.), and the phylum Bacillota (Firmicutes) play a protective role in HC. Staphylococcus epidermidis, Corynebacterium (unc.), the family Neisseriaceae, and Pasteurellaceae sp. were associated with an increased risk of HC. Conclusion: This study provided new evidence regarding the association between skin microbiota and PLC, suggesting that skin microbiota plays a role in PLC progression. Skin microbiota could be a novel and effective way for PLC diagnosis and treatment.