Exploring the causal relationship between gallbladder removal and irritable bowel syndrome

Abstract

Background: Clinical evidence strongly suggests a correlation between gallbladder removal (cholecystectomy) and irritable bowel syndrome (IBS), though the exact causal relationship remains uncertain. Our objective is to clarify this causality bidirectionally using Mendelian Randomization (MR), shedding light on the relationship between cholecystectomy and IBS. Methods: We accessed GWAS summary datasets on cholecystectomy and IBS from public repositories. Our MR analysis primarily utilized the inverse-variance weighting (IVW) technique, supplemented by sensitivity analyses to address heterogeneity and pleiotropy concerns. Additionally, a reverse MR analysis was conducted to explore potential reverse causation. Results: Our forward MR analysis identified a statistically significant association between genetically predicted cholecystectomy and increased risk of IBS (IVW OR 3.056; 95 % CI: 1.081–8.641, p = 0.035). Conversely, the reverse MR indicated that genetic predisposition to IBS may also influence the risk of cholecystectomy (IVW OR 1.007; 95 % CI: 1.002–1.011, p = 0.0019). Conclusions: Our genetic epidemiological approach strengthens evidence for causal relationships between cholecystectomy and IBS, with reciprocal findings from the reverse MR analysis suggesting bidirectional influences. Nonetheless, confirming these findings through clinical and experimental studies is crucial.

Keywords

• Irritable bowel syndrome
• Gallbladder removal
• Cholecystectomy
• Mendelian randomization
• Single nucleotide polymorphism