【摘要】 目的 探讨炎症性肠病（IBD）与20种感染性疾病之间的因果关系，并分析糖皮质激素和免疫抑制剂的中介效应。方法 基于全基因组关联研究汇总数据，采用双向双样本孟德尔随机化（MR）评估IBD、溃疡性结肠炎（UC）和克罗恩病（CD）与20种感染性疾病的双向因果效应；运用两步法MR评估药物中介效应。以逆方差加权法（IVW）为核心，辅以MR-Egger、加权中位数、加权模式法等方法验证，采用Cochran’s Q、MR-PRESSO、MR Steiger及留一法进行敏感性分析，结果经Benjamini-Hochberg多重校正。结果 经多重检验校正后，发现IBD(OR=1.159,95%CI:1.092～1.230)和UC(OR=1.157,95%CI:1.093～1.225)与艰难梭菌感染风险增加显著相关[均错误发现率（FDR）<0.05]。CD与丙型肝炎病毒感染风险加大相关（OR=1.143,95%CI:1.052～1.241,FDR<0.05）。两步法MR分析未发现糖皮质激素和免疫抑制剂在上述因果关系中发挥显著的中介效应。结论 IBD与特定感染性疾病存在显著因果关系，提示临床应重视IBD患者的机会性感染风险管理，并进一步探究病毒暴露在IBD发病中的潜在机制。更多还原

【Abstract】 Objective To investigate the causal associations between inflammatory bowel disease(IBD) and 20 infectious diseases, and to analyze the mediating effects of glucocorticoids and immunosuppressants. Methods Based on genome-wide association study(GWAS) summary data, a bidirectional two-sample Mendelian randomization(MR) approach was employed to evaluate the causal effects between IBD, ulcerative colitis(UC), Crohn’s disease(CD), and 20 infectious diseases. A two-step MR was utilized to assess the mediating effects of medications. The inverse-variance weighted(IVW)method was used as the primary analysis, complemented by MR-Egger, weighted median, and weighted mode methods for validation. Sensitivity analyses were performed using Cochran’s Q test, MR-PRESSO, MR Steiger test, and leave-one-out analysis. The results were adjusted for multiple testing using the Benjamini-Hochberg procedure. Results After multiple testing correction, both IBD(OR=1.159, 95% CI: 1.092-1.230) and UC(OR=1.157, 95% CI: 1.093-1.225) were significantly associated with an increased risk of Clostridioides difficile infection(both FDR<0.05). CD was associated with a higher risk of hepatitis C virus infection(OR=1.143, 95%CI: 1.052-1.241, FDR<0.05). Furthermore, the two-step MR analysis revealed no significant mediating effects of glucocorticoids and immunosuppressants in these causal associations. Conclusion Significant causal associations exist between IBD and specific infectious diseases. This highlights the necessity for clinical vigilance regarding opportunistic infection risk management in patients with IBD, and warrants further investigation into the potential mechanisms of viral exposure in IBD pathogenesis.更多还原