Gut microbiota, colorectal cancer, and metastatic liver cancer: A Mendelian randomization analysis

Increasing evidence suggests associations between gut microbiota composition and colorectal cancer (CRC) or hepatocellular carcinoma. However, whether gut microbiota influences metastatic liver cancer (MLC) originating from CRC remains unclear. We performed a bidirectional 2-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies. Gut microbiota data (N = 18,340) from MiBioGen served as exposures. MLC (N = 463,010) and CRC (N = 399,920) datasets were sourced from IEU OpenGWAS. The correlation analysis was primarily conducted using the inverse variance weighted method, which demonstrated reliability as confirmed through sensitivity analysis. Inverse variance weighted estimates indicated that class_Actinobacteria showed an inverse association with MLC (odds ratio [OR] = 0.997, 95% confidence interval [CI]: 0.995-0.999, P = .003), while class_Melainabacteria exhibited a positive association (OR = 1.001, 95% CI: 1.000-1.002, P = .011). For CRC, both class_Actinobacteria (OR = 0.992, 95% CI: 0.986-0.997, P = .005) and order_Bifidobacteriales (OR = 0.991, 95% CI: 0.986-0.997, P = .003) demonstrated inverse associations. Notably, MR estimates revealed that class_Actinobacteria had consistently inverse associations with both MLC and CRC. Reverse MR analysis suggested CRC may increase abundance of family_BacteroidalesS24.7group (OR = 4.178, 95% CI: 3.233-6.304, P = .002), but no significant associations were observed for MLC. This study provides novel evidence supporting potential causal associations between specific gut microbial taxa and the risk of MLC, suggesting a possible protective role of Actinobacteria in the pathogenesis of both MLC and CRC. Further large-scale observational and mechanistic studies are warranted to clarify these relationships.