Association between gut microbiota and hepatocellular carcinoma and biliary tract cancer: A mendelian randomization study

Abstract

BACKGROUND An increasing number of studies have begun to discuss the relationship between gut microbiota and diseases, yet there is currently a lack of corresponding articles describing the association between gut microbiota and hepatocellular carcinoma (HCC) and biliary tract cancer (BTC). This study aims to explore the relationship between them using Mendelian randomization (MR) analysis method. AIM To assess the relationship between gut microbiota and HCC and BTC. METHODS We obtained Genome-wide association study (GWAS) data for the gut microbiome from the intestinal microbiota genomic library (MiBioGen, https://mibiogen.gcc.rug.nl/ ). Additionally, we accessed data pertaining to HCC and BTC from the IEU open GWAS platform (https://gwas.mrcieu.ac.uk/ ). Our analysis employed fundamental instrumental variable analysis methods, including inverse-variance weighted, MR and Egger. To ensure the dependability of the results, we subjected the results to tests for multiple biases and heterogeneity. RESULTS During our investigation, we discovered 11 gut microbiota linked to an increased risk to BTC and HCC. The former included the genus Eubacterium hallii group (P = 0.017), Candidatus Soleaferrea (P = 0.034), Flavonifractor (P = 0.021), Lachnospiraceae FCS020 (P = 0.034), the order Victivallales (P = 0.018), and the class Lentisphaeria (P = 0.0.18). The latter included the genus Desulfovibrio (P = 0.042), Oscillibacter (P = 0.023), the family Coriobacteriaceae (P = 0.048), the order Coriobacteriales (P = 0.048), and the class Coriobacteriia (P = 0.048). Furthermore, in BTC, we observed 2 protective gut microbiota namely the genus Dorea (P = 0.041) and Lachnospiraceae ND3007 group (P = 0.045). All results showed no evidence of multiplicity or heterogeneity. CONCLUSION This study explores a causal link between gut microbiota and HCC and BTC. These insights may enhance the mechanistic knowledge of microbiota-related HCC and BTC pathways, potentially informing therapeutic strategies.