Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1319
Peer-review started: October 23, 2023
First decision: December 12, 2023
Revised: December 20, 2023
Accepted: January 15, 2024
Article in press: January 15, 2024
Published online: April 15, 2024
Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with poor prognosis. Previous studies have implicated the gut microbiota in CCA, but evidence for causal mechanisms is lacking.
To investigate the causal relationship between gut microbiota and CCA risk.
To investigate the causal relationship between gut microbiota and CCA risk.
We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA. Genetic variants were used as instrumental variables. Multiple sensitivity analyses assessed result robustness.
Fifteen gut microbial taxa showed significant causal associations with CCA risk. Higher genetically predicted abundance of genus Eubacteriumnodatum group, Genus Ruminococcustorques group, Coprococcus, Dorea, and Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA. Increased intrahepatic CCA risk was associated with higher abundance of Veillonellaceae, Alistipes, Enterobacteriales, and Firmicutes. Protective effects against CCA were suggested for Collinsella, Eisenbergiella, Anaerostipes, Paraprevotella, Parasutterella, and Verrucomicrobia. Sensitivity analyses indicated these findings were reliable without pleiotropy.
This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk. Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.
Experimental validation of the candidate microbes identified to be causally associated with CCA risk. Further in vitro and in vivo studies could be conducted to consolidate the causal effects and explore the underlying molecular mechanisms. Analysis of species-level resolution of gut microbiota through metagenomic shotgun sequencing or other techniques. The current study was limited to genus-level associations due to 16S rRNA gene sequencing. A more detailed characterization at the species level could provide further insights.