A dose-dependent increase in the risk of inflammatory bowel disease after exposure to broad-spectrum antibiotics: A national population study in Korea.

Abstract

The association between antibiotic use and risk of inflammatory bowel disease (IBD), particularly among adults, remains unclear. Furthermore, there is a scarcity of data among non-Western countries. To investigate the association and dose-response relationships between antibiotic use and subsequent IBD risk across all ages METHODS: This population-based case-control analysis used data from the Korean National Health Insurance Service database (2004-2018). We compared 68,633 patients with new-onset IBD to matched controls (n = 343,165) using multivariable conditional logistic regression analysis. We also examined the dose-response relationship using non-linear regression analysis, and separately analysed childhood-onset IBD (aged ≤14 years) risk following early-life antibiotic exposure. The mean age at diagnosis was 45.2 ± 16.8 years. Antibiotic prescriptions between 2 and 5 years before diagnosis significantly increased the odds of developing IBD (adjusted odds ratio [OR], 1.24; 95% confidence interval [CI]: 1.21-1.27). Additionally, sensitivity analysis revealed an elevated risk up to 9 years before diagnosis. Broad-spectrum antibiotics increased IBD risk, independent of gastroenteritis. A distinct dose-response relationship was observed irrespective of the IBD subtype and study population (all p < 0.001). Furthermore, antibiotic exposure within the first year of life was linked with the risk of childhood-onset IBD (OR, 1.51; 95% CI: 1.25-1.82). Broad-spectrum antibiotics dose-dependently increased the risk for IBD in the Korean population. Our findings provide a fundamental epidemiological basis for identifying antibiotic use as a significant risk factor for IBD across different environmental backgrounds.