Supplementary Material for: Do Antibiotics Cause Inflammatory Bowel Disease? A Systematic Review and Meta-Analysis.

Introduction: Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), exhibits a multifactorial pathogenesis influenced by genetic and environmental factors. Antibiotic usage has been implicated in modifying the gut microbiome, potentially leading to dysbiosis and contributing to IBD risk. Despite existing literature, the relationship remains inconclusive. This meta-analysis aimed to evaluate the association between prior antibiotic use and the onset of IBD.

Methods: A systematic literature search in PubMed was conducted to identify studies exploring the link between antibiotic use and subsequent IBD diagnosis. Studies reporting CD, UC, or both as primary outcomes were included. The meta-analysis, performed according to PRISMA guidelines, summarized risk estimates, represented as odds ratios (OR), and corresponding confidence intervals (CI). Subgroup analyses involved the categorization of antibiotics and the determination of the minimum number of antibiotic therapy courses administered.

Results: Out of 722 publications, 31 studies comprising 102,103 individuals met eligibility criteria. The pooled OR for IBD in those with prior antibiotic exposure was 1.40 (95% CI: 1.25-1.56). Antibiotic use was associated with an increased risk of IBD (OR 1.52, 95% CI: 1.19-1.94). Notably, this association was confined to CD (OR 1.50, 95% CI: 1.27-1.77), while no significant association was observed with UC (OR 1.21, 95% CI: 1.00-1.47). Risk augmentation for IBD correlated positively with the number of antibiotic courses (OR 1.08, 95% CI: 1.05-1.12).

Conclusion: Previous antibiotic use is associated with the later development of CD. A positive dose-response effect was also observed. Against this background, antibiotics should be used rationally.