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

This study investigated the causal effect of physical activity (PA) on inflammatory bowel disease (IBD) and the role of body mass index (BMI) as a mediator. We used instrumental variables for moderate to vigorous physical activity (MVPA) during leisure time and leisure screen time (LST) derived from genome-wide association studies (GWASs) meta-analysis. IBD, Crohn’s disease (CD), and ulcerative colitis (UC) summary statistics were sourced from GWASs on European populations. We conducted univariable Mendelian randomization (UVMR) to assess the direct impacts of MVPA and LST on IBD risk. Multivariable Mendelian randomization (MVMR) was used to evaluate the mediating effects of BMI. Results indicated a protective effect of MVPA against IBD and CD. Conversely, higher genetically-predicted LST correlated with increased IBD and CD risks. BMI mediated 0.8% and 3.7% of the LST effect on IBD/CD, respectively, and 3.5% and 11.0% of the MVPA effect. Thus, PA appears causally related to lower IBD/CD risk, with BMI partially mediating this relationship, highlighting the risk increase from reduced PA via elevated BMI. Key messages What 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.