The causal effects of primary biliary cholangitis on irritable bowel syndrome: a mendelian randomization study.

BACKGROUND

The gut-liver axis indicates a potential relationship between the primary biliary cholangitis (PBC) and irritable bowel syndrome (IBS). Nonetheless, the causality of this association remains unclear. This study performed a two-sample Mendelian randomization (MR) approach to investigate the causal relationship between the PBC and IBS.

METHODS

We used public genome-wide association study (GWAS) datasets for PBC and IBS, treating PBC as the exposure and IBS as the outcome, in an MR analysis primarily employing the inverse-variance weighted (IVW) method. Sensitivity analyses and pleiotropy/heterogeneity tests were conducted to ensure finding robustness, validating trait-specific genetic associations and consistent variant effects, enhancing study credibility.

RESULTS

Findings encompassed the selection of 15 valid instrumental variables (IVs) for PBC and 18 for IBS. The MR analyses uncovered a statistically significant link, suggesting that PBC is positively correlated with an increased likelihood of IBS development (IVW odds ratio: 1.010887; 95% confidence interval: 1.0004241 to 1.021459; P -value = 0.04136). Deeper investigation through MR-Egger regression analysis indicated negligible probability of result distortion due to directional pleiotropy (regression intercept: 0.001207003; P -value = 0.7193585). Consistency was further corroborated by Cochran's Q test and funnel plot inspections, which displayed no signs of heterogeneity ( P = 0.5410849) or asymmetry, reinforcing the absence of detrimental pleiotropic influences.

CONCLUSIONS

Our study provides evidence of a potential causal link between PBC and increased IBS risk, highlighting the need for further research to explore the mechanisms underlying this complex disease relationship.