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

Background: The association between antibiotic use and inflammatory bowel disease (IBD) risk, particularly among adults, remains unclear. Further, there is a scarcity of data among non-Western countries. Aims: This study aimed 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 their matched controls (n = 343,165) using multivariable conditional logistic regression analysis. Further, we 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. Results: The mean age at diagnosis was 45.2 +/- 16.8 years. Antibiotic prescriptions between 2 and 5 years before diagnosis, indicated by antibiotic prescriptions, significantly increased the odds of developing IBD by approximately 24% (adjusted odds ratio [OR], 1.24; 95% confidence interval [CI]: 1.21-1.27). Additionally, a 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 childhood-onset IBD risk (OR, 1.51; 95% CI: 1.25-1.82). Conclusions: Broad-spectrum antibiotics dose-dependently increased the risk for IBD in the national population. Our findings provide a fundamental epidemiological basis for identifying antibiotic use as a significant risk factor for IBD across different environmental backgrounds.

Automated summary

This study aimed to investigate the association and dose-response relationships between antibiotic use and subsequent inflammatory bowel disease (IBD) risk in the Korean population. The findings revealed that antibiotic prescriptions 2-5 years prior to diagnosis significantly increased the odds of developing IBD, and early-life antibiotic exposure was linked with childhood-onset IBD risk. These findings establish antibiotic use as a significant risk factor for IBD across different environmental backgrounds.