Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Gastroenterology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Front Immunol. 2024 Feb 21;15:1327503. doi: 10.3389/fimmu.2024.1327503. eCollection 2024.
Numerous observational studies have identified a linkage between the gut microbiota and gastroesophageal reflux disease (GERD). However, a clear causative association between the gut microbiota and GERD has yet to be definitively ascertained, given the presence of confounding variables.
The genome-wide association study (GWAS) pertaining to the microbiome, conducted by the MiBioGen consortium and comprising 18,340 samples from 24 population-based cohorts, served as the exposure dataset. Summary-level data for GERD were obtained from a recent publicly available genome-wide association involving 78 707 GERD cases and 288 734 controls of European descent. The inverse variance-weighted (IVW) method was performed as a primary analysis, the other four methods were used as supporting analyses. Furthermore, sensitivity analyses encompassing Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and leave-one-out methodology were carried out to identify potential heterogeneity and horizontal pleiotropy. Ultimately, a reverse MR assessment was conducted to investigate the potential for reverse causation.
The IVW method's findings suggested protective roles against GERD for the ( = 0.027), (P = 0.026), ( = 0.026), and (P = 0.019). In contrast, ( = 0.037), (P = 0.049), and ( = 0.024) emerged as potential GERD risk factors. In assessing reverse causation with GERD as the exposure and gut microbiota as the outcome, the findings indicate that GERD leads to dysbiosis in 13 distinct gut microbiota classes. The MR results' reliability was confirmed by thorough assessments of heterogeneity and pleiotropy.
For the first time, the MR analysis indicates a genetic link between gut microbiota abundance changes and GERD risk. This not only substantiates the potential of intestinal microecological therapy for GERD, but also establishes a basis for advanced research into the role of intestinal microbiota in the etiology of GERD.
许多观察性研究已经发现肠道微生物群与胃食管反流病（GERD）之间存在联系。然而，由于存在混杂变量，肠道微生物群与 GERD 之间是否存在明确的因果关系仍未确定。
MiBioGen 联盟进行的全基因组关联研究（GWAS）涉及微生物组，该研究包含来自 24 个人群队列的 18340 个样本，作为暴露数据集。GERD 的汇总水平数据来自最近一项公开的全基因组关联研究，该研究涉及 78707 例 GERD 病例和 288734 例欧洲血统对照。作为主要分析，采用逆方差加权（IVW）方法，其他四种方法作为支持分析。此外，进行了 Cochran's Q 统计、MR-Egger 截距、MR-PRESSO 全局检验和逐一排除方法的敏感性分析，以识别潜在的异质性和水平多效性。最终，进行了反向 MR 评估，以研究潜在的反向因果关系。
IVW 方法的结果表明， （ = 0.027）、 （P = 0.026）、 （ = 0.026）和 （P = 0.019）对 GERD 具有保护作用。相比之下， （ = 0.037）、 （P = 0.049）和 （ = 0.024）则成为 GERD 的潜在风险因素。在将 GERD 作为暴露因素和肠道微生物群作为结果进行反向因果关系评估时，研究结果表明，GERD 导致 13 种不同的肠道微生物群类别的失调。通过对异质性和多效性进行彻底评估，MR 结果的可靠性得到了确认。
首次通过 MR 分析表明，肠道微生物群丰度变化与 GERD 风险之间存在遗传联系。这不仅证实了肠道微生态疗法治疗 GERD 的潜力，也为深入研究肠道微生物在 GERD 发病机制中的作用奠定了基础。
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