Risk of Inflammatory Bowel Disease Following Hospital‐Treated Infections and Modulatory Role of Host Genetics to Support a Multi‐Hit Pathogenesis Model

Infectious diseases can cause lasting immune disturbances, but whether they contribute to later inflammatory bowel disease (IBD) is unclear. Hospital‐treated infections may be especially informative because they reflect substantial immune challenge, yet their relation to IBD risk and the role of host genetics remain poorly defined. It examines hospital‐treated infections and incident IBD in a prospective cohort and integrates gene‐environment interaction analyses to identify susceptibility pathways and develop a post‐infection risk score. Hospital‐treated infections of multiple pathogen types and sites were associated with higher subsequent IBD risk. This association is stronger in carriers of immune‐related risk variants, with Crohn’s disease linked mainly to innate immune and autophagy pathways and ulcerative colitis to JAK‐STAT, T‐cell differentiation, and chemokine signaling. An Infection IBD Score based on 44 immune‐related genes stratified post‐infection risk. These findings support infections as triggers of IBD in genetically susceptible individuals and highlight a potential tool for risk stratification.