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.