Abstract:Objective To investigate the causal relationship between circadian rhythm disruption and inflammatory bowel disease (IBD) and the mediating effect of gut microbiota based on Mendelian randomization (MR). Methods Summary statistics of Genome-wide Association Study (GWAS) for circadian rhythm disruption (n=205 527) and IBD (n=214 053) were obtained from IEU OpenGWAS database. Summary statistics of GWAS for the gut microbiota were obtained from the MiBioGen database (n=18 340). Two-sample MR analysis was used to estimate the genetic correlation and causality between circadian rhythm disruption and IBD, and the mediating effect of the gut microbiota was analyzed by two-step MR analysis. Results There was a suggestive causal relationship between circadian rhythm disruption and IBD (odds ratio=1.255, P<0.05). Rikenellaceae id.967 played a mediating role in the causal chain between them (the mediating effect was -0.028 740). Sensitivity analysis confirmed that the results were not interfered by level pleiotropy and heterogeneity. Conclusion There is a genetic correlation between circadian rhythm disruption and IBD, and gut microbiota may play a mediating role between them.