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.

引言：炎症性肠病（Inflammatory Bowel Disease, IBD）涵盖克罗恩病（Crohn's Disease, CD）与溃疡性结肠炎（Ulcerative Colitis, UC），其发病机制为多因素共同参与的复杂过程，受遗传与环境因素交互影响。抗生素使用被认为可改变肠道微生物组结构，有可能引发菌群失调，进而增加IBD的发病风险。尽管已有相关研究报道，但二者间的关联仍未达成共识。本荟萃分析旨在评估既往抗生素使用与IBD发病的相关性。

方法：在PubMed数据库中开展系统性文献检索，筛选探讨抗生素使用与后续IBD诊断关联的研究。纳入以CD、UC或二者为主要结局指标的相关研究。本荟萃分析遵循PRISMA指南进行，汇总以比值比（Odds Ratio, OR）及对应置信区间（Confidence Interval, CI）表示的风险估计值。亚组分析按抗生素类别进行分类，并明确抗生素治疗疗程的最小使用数量。

结果：在检索到的722篇文献中，共有31项符合纳入标准的研究，涉及102103名研究对象。既往有抗生素暴露史人群的IBD合并比值比为1.40（95%CI：1.25~1.56）。抗生素使用与IBD风险升高显著相关（OR=1.52，95%CI：1.19~1.94）。值得注意的是，该关联仅见于CD患者（OR=1.50，95%CI：1.27~1.77），而UC未观察到显著关联（OR=1.21，95%CI：1.00~1.47）。IBD的发病风险升高与抗生素疗程数呈正相关（OR=1.08，95%CI：1.05~1.12）。

结论：既往抗生素使用与后续CD的发生存在显著关联，同时还观察到明确的剂量-反应效应。基于上述研究结果，临床应合理使用抗生素。