Abstract
This study aims to investigate the causal relationship between gut microbiota and Crohn disease (CD) and identify and quantify the role of metabolites as potential mediators. Using summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of genetically predicted gut microbiota and CD was performed. Furthermore, we used two-step MR to quantify the proportion of the effect of metabolites-mediated gut microbiota on CD. We identified 15 metabolites (carnitine levels, isovalerate (i5:0) levels, hydroxyoctanoate levels, 6-hydroxyindole sulfate levels, heptenedioate, 4-methylhexanoylglutamine levels, uridine levels, X-13866 levels, X-17354 levels, X-18345 levels, X-22834 levels, X-25519 levels, serine to pyruvate ratio, URIDINE to 2'-deoxyuridine ratio, and histidine to glutamine ratio) with mediating effects in the impact of genus Ruminococcaceae UCG013 on CD. Our study identified a causal relationship between gut microbiota and CD, with a small proportion of the effect mediated by fifteen metabolites.