Deciphering the complex interplay between physical activity, inflammatory bowel disease and obesity/BMl through causal inference and mediation analyses

Abstract

AbstractBackground and AimsObservational studies on the association between physical activity (PA) and inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), report inconsistent results. Moreover, the underlying mediator between PA and IBDs remains unknown. We aimed to investigate the causal effect of PA on IBD and the role of BMI as a mediator between PA and IBD.MethodsInstrumental variables for the main exposures, i.e., moderate to vigorous intense PA during leisure time (MVPA) and leisure screen time (LST), were extracted from the meta-analysis on genome-wide association studies (GWASs). Summary statistics of IBD, CD, and UC were retrieved from the GWASs on European populations. Univariable Mendelian randomization (UVMR) analysis was performed to investigate the net and individual effects of MVPA and LST on the risk of IBD. Multivariate MR analysis was performed to investigate the effect of mediators on the risk of IBD.ResultsMR analysis revealed a protective relationship between MVPA and the risk of IBD and CD. Higher genetically-predicted LST was associated with increased risk of IBD and CD. The proportion of the effect of LST on IBD/CD mediated by BMI was determined to be 0.8% and 3.7%. The proportion of the effect of MVPA on IBD/CD mediated by BMI was determined to be 3.5% and 11.0%.ConclusionOur findings indicate a causal relationship between PA and IBD/CD and elucidate the increased risk of IBD/CD due to reduced PA is partially mediated by increased BMI.Key messagesWhat is already known?Observational studies have shown that occupations involving more physical labor are associated with a lower risk of IBD compared with sedentary occupations.What is new here?The causal effect of PA on IBD and the role of BMI as a mediator between PA and IBD were investigated.How can this study help patient care?The incidence of CD can be reduced by promoting lifestyle management, such as reducing recreational sedentary activities and encouraging proper exercise. In addition, individuals who are not physically active should monitor their BMI to prevent the development of CD.