Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Front Immunol. 2024 May 8;15:1365604. doi: 10.3389/fimmu.2024.1365604. eCollection 2024.
Observational studies have indicated a possible connection between Helicobacter pylori (H. pylori) infection and eosinophilic esophagitis (EoE), but their causal relationship has yet to be established. To investigate the causal associations between H. pylori infection and EoE, we performed a Mendelian randomization (MR) analysis.
Firstly, we conducted both univariable and multivariable Mendelian randomization (MR) analyses. Furthermore, a two-step MR was carried out to ascertain the potential underlying pathways of these associations, particularly the involvement of inflammatory cytokines. We employed the inverse-variance weighted (IVW) method as the main analysis in our MR study. To enhance the credibility of the results, we also conducted several sensitivity analyses.
Our study demonstrated a noteworthy correlation between genetically predicted anti-H. pylori IgG antibody levels and a reduced risk of EoE (OR=0.325, 95% CI=0.165-0.643, P value=0.004, adj p value=0.009). No significant causal associations were detected between other H. pylori antibodies and EoE in our study. When it comes to multivariable MR analysis controlling for education attainment, household income, and deprivation individually, the independent causal impact of anti-H. pylori IgG on EoE persisted. Surprisingly, the two-step MR analysis indicated that inflammatory factors (IL-4, IL-5, IL-13, IL-17, and IFN-γ) did not appear to mediate the protective effect of H. pylori infection against EoE.
Findings suggested that among the range of H. pylori-related antibodies, anti-H. pylori IgG antibody is the sole causal factor associated with protection against EoE. Certain inflammatory factors may not be involved in mediating this association. These findings make a significant contribution to advancing our understanding of the pathogenesis of EoE and its evolving etiology.
观察性研究表明，幽门螺杆菌（H. pylori）感染与嗜酸性食管炎（EoE）之间可能存在关联，但它们之间的因果关系尚未确定。为了研究 H. pylori 感染与 EoE 之间的因果关系，我们进行了孟德尔随机化（MR）分析。
首先，我们进行了单变量和多变量孟德尔随机化（MR）分析。此外，还进行了两步 MR 分析，以确定这些关联的潜在潜在途径，特别是炎症细胞因子的参与。我们采用逆方差加权（IVW）方法作为 MR 研究的主要分析方法。为了提高结果的可信度，我们还进行了几项敏感性分析。
我们的研究表明，遗传预测的抗 H. pylori IgG 抗体水平与 EoE 风险降低之间存在显著相关性（OR=0.325，95%CI=0.165-0.643，P 值=0.004，调整后 P 值=0.009）。在我们的研究中，没有发现其他 H. pylori 抗体与 EoE 之间存在显著的因果关系。在多变量 MR 分析中，当单独控制教育程度、家庭收入和贫困程度时，抗 H. pylori IgG 对 EoE 的独立因果作用仍然存在。令人惊讶的是，两步 MR 分析表明，炎症因子（IL-4、IL-5、IL-13、IL-17 和 IFN-γ）似乎并未介导 H. pylori 感染对 EoE 的保护作用。
研究结果表明，在一系列与 H. pylori 相关的抗体中，抗 H. pylori IgG 抗体是唯一与 EoE 保护相关的因果因素。某些炎症因子可能不参与介导这种关联。这些发现为深入了解 EoE 的发病机制及其不断变化的病因学做出了重要贡献。
