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.