Department of Gynaecology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China.
Department of Oncology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China.
J Obstet Gynaecol. 2024 Dec;44(1):2362415. doi: 10.1080/01443615.2024.2362415. Epub 2024 Jun 17.
Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship of the association remains to be investigated.
Genome-wide association study (GWAS) data of GM was obtained from the MiBioGen consortium, and GWAS for endometriosis data was from the FinnGen consortium. Initially, a two-sample Mendelian randomisation (MR) analysis was performed to identify specific bacteria associated with endometriosis. Inverse variance-weighted (IVW) was used as the main MR analysis to infer causal relationships. The other four popular MR methods including MR-Egger regression, weighted mode, weighted median, and simple mode were used for secondary confirmation. Subsequently, these selected bacteria were employed as exposure to investigate their causal effects on six sub-types of endometriosis. Furthermore, reverse MR analysis was implemented to evaluate the reverse causal effects. Cochran's Q statistics was used to test the heterogeneity of instrumental variables (IVs); MR-Egger regression was used to test horizontal pleiotropy; MR-PRESSO and leave-one-out sensitivity analysis were applied to find significant outliers.
A total of 1131 single nucleotide polymorphisms (SNPs) were collected as IVs for 196 GM taxa with endometriosis as the outcome. We identified 12 causal relationships between endometriosis and GM taxa including 1 phylum, 3 families, 2 orders, and 6 genera (Rikenellaceae RC9 gut group, Eubacterium ruminantium group, Faecalibacterium, Peptococcus, Clostridium sensu stricto 1, and Ruminococcaceae UCG005). Utilizing the Bonferroni method, we identified phylum Cyanobacteria as the strongest associated GM taxa. Subsequently, 6 significant causal effects were uncovered between the 12 selected specific GM and 6 sub-types of endometriosis. Meanwhile, no reverse causal relationship was found. Further, no horizontal pleiotropy and no significant outliers were detected in the sensitive analysis.
This MR analysis revealed significant causal effects between GM and endometriosis and phylum Cyanobacteria had the strongest association.
先前的观察性证据表明，肠道微生物群（GM）可能参与子宫内膜异位症的发生。然而，这种关联的因果关系仍有待研究。
从 MiBioGen 联盟获得 GM 的全基因组关联研究（GWAS）数据，从 FinnGen 联盟获得子宫内膜异位症的 GWAS 数据。最初，进行了两样本孟德尔随机化（MR）分析，以确定与子宫内膜异位症相关的特定细菌。使用逆方差加权（IVW）作为主要 MR 分析来推断因果关系。其他四种常用的 MR 方法，包括 MR-Egger 回归、加权模式、加权中位数和简单模式，用于二次确认。随后，将这些选定的细菌用作暴露因素，以研究它们对子宫内膜异位症六种亚类的因果作用。此外，进行了反向 MR 分析以评估反向因果作用。Cochran's Q 统计量用于检验工具变量（IVs）的异质性；MR-Egger 回归用于检验水平多效性；MR-PRESSO 和单样本剔除敏感性分析用于发现显著的离群值。
共收集了 1131 个单核苷酸多态性（SNPs）作为 IVs，用于分析与子宫内膜异位症相关的 196 种 GM 分类群。我们确定了 12 种与 GM 分类群与子宫内膜异位症之间的因果关系，包括 1 个门、3 个科、2 个目和 6 个属（Rikenellaceae RC9 肠道群、Eubacterium ruminantium 群、Faecalibacterium、Peptococcus、Clostridium sensu stricto 1 和 Ruminococcaceae UCG005）。利用 Bonferroni 方法，我们确定了门蓝细菌是最强相关的 GM 分类群。随后，在 12 种选定的特定 GM 与 6 种子宫内膜异位症亚类之间发现了 6 种显著的因果作用。同时，在敏感分析中未发现反向因果关系。此外，未检测到水平多效性和显著的离群值。
这项 MR 分析表明 GM 与子宫内膜异位症之间存在显著的因果关系，并且门蓝细菌具有最强的相关性。
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