Deciphering potential significances of biliary microbiome in cholelithiasis and cholangiocarcinoma

This study aims to investigate the role of biliary microbiota (defined as the microbial community colonizing the biliary tract, including the gallbladder, intrahepatic and extrahepatic bile ducts) in the pathogenesis of cholelithiasis (CHOL) and cholangiocarcinoma (CCA), with a focus on the associations between microbial communities and these biliary diseases.

We conducted a comprehensive bioinformatics analysis using high-throughput sequencing data obtained from the Sequence Read Archive (SRA) database to characterize the composition of microbial communities in patients with CCA and CHOL. We performed operational taxonomic unit (OTU) clustering, statistical analyses and Mendelian randomization (MR) to elucidate the causal relationships between specific bacterial strains and disease outcomes.

Our findings revealed differences in the relative abundance of specific microbial taxa among research groups. The CCA + CHOL group exhibited a significant increase in the abundance of Fusobacteria, particularly Fusobacterium, compared to the Control or CCA group. This suggests a potential pathogenic role for these microorganisms in CHOL formation. Additionally, the CCA group demonstrated a higher diversity index, indicating that increased microbial diversity may contribute to the progression of the disease. MR analysis identified nominally significant statistical associations between specific bacterial strains. However, the presence of pleiotropy in some analyses necessitates caution when interpreting causal relationships.

Our study highlights the complex interplay between biliary microbiota and the pathogenesis of CHOL and CCA. Modulating biliary microbiota may represent a promising therapeutic strategy for managing these diseases. Future research should focus on the functional roles of specific taxa in bile metabolism and immune modulation, ultimately improving our understanding of biliary health and disease management.