Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Acta Obstet Gynecol Scand. 2024 Nov;103(11):2232-2241. doi: 10.1111/aogs.14957. Epub 2024 Sep 10.
Previous studies have established a link between gut microbiota and polycystic ovary syndrome (PCOS), but little is known about their precise causal relationship. Therefore, this study aims to explore whether there are precise causal relationships between gut microbiota and PCOS.
We performed a bidirectional two-sample Mendelian randomization (MR) analysis. Datasets were from the largest published meta-analysis on gut microbiota composition and the FinnGen cohort of the IEU Open Genome-Wide Association Study Project database. Inverse variance weighted (IVW), MR-Egger, constrained maximum likelihood-based Mendelian randomization, weighted median, weighted mode, and simple mode were used. Cochran's Q and MR-Egger intercept tests were employed to measure the heterogeneity.
A total of 211 gut microbiota taxa were identified in MR analysis. Nine taxa of bacteria, including Alphaproteobacteria (0.55, 0.30-0.99, p = 0.04), Bacilli (1.76, 1.07-2.91, p = 0.03), Bilophila (0.42, 0.23-0.77, p < 0.01), Blautia (0.16, 0.03-0.79, p = 0.02), Burkholderiales (2.37, 1.22-4.62, p = 0.01), Candidatus Soleaferrea (0.65, 0.43-0.98, p = 0.04), Cyanobacteria (0.51, 0.31-0.83, p = 0.01), Holdemania (0.53, 0.35-0.81, p < 0.01), and Lachnospiraceae (1.86, 1.04-3.35, p = 0.03), were found to be associated with PCOS in the above MR methods included at least IVW method. Cochran's Q statistics and MR-Egger intercept test suggested no significant heterogeneity. In addition, 69 taxa were shown significant for at least the IVW method in reverse MR analysis, of these, 25 had a positive correlation, and 37 had a negative correlation. Additionally, Alphaproteobacteria and Lachnospiraceae (0.95, 0.91-0.98, p < 0.01; 0.97, 0.94-0.99, p = 0.02, respectively) were shown a bidirected causally association with PCOS.
Our study provides evidence of the bidirectional causal association between gut microbiota and PCOS from a genetic perspective.
先前的研究已经证实了肠道微生物群与多囊卵巢综合征(PCOS)之间存在关联,但它们之间的确切因果关系尚不清楚。因此,本研究旨在探讨肠道微生物群与 PCOS 之间是否存在确切的因果关系。
我们进行了双向双向孟德尔随机化(MR)分析。数据集来自于最大的已发表的肠道微生物群组成的荟萃分析和 IEU 开放基因组全基因组关联研究项目数据库的芬兰队列。采用逆方差加权(IVW)、MR-Egger、基于约束极大似然的孟德尔随机化、加权中位数、加权模式和简单模式。采用 Cochran's Q 和 MR-Egger 截距检验来衡量异质性。
在 MR 分析中总共鉴定出 211 种肠道微生物群分类群。9 种细菌,包括 Alphaproteobacteria(0.55,0.30-0.99,p=0.04)、Bacilli(1.76,1.07-2.91,p=0.03)、Bilophila(0.42,0.23-0.77,p<0.01)、Blautia(0.16,0.03-0.79,p=0.02)、Burkholderiales(2.37,1.22-4.62,p=0.01)、Candidatus Soleaferrea(0.65,0.43-0.98,p=0.04)、Cyanobacteria(0.51,0.31-0.83,p=0.01)、Holdemania(0.53,0.35-0.81,p<0.01)和 Lachnospiraceae(1.86,1.04-3.35,p=0.03)与 PCOS 相关。在至少包含 IVW 方法的上述 MR 方法中发现了这 9 种细菌与 PCOS 相关。Cochran's Q 统计量和 MR-Egger 截距检验表明没有显著的异质性。此外,在反向 MR 分析中,至少有 69 种分类群与 IVW 方法显著相关,其中 25 种呈正相关,37 种呈负相关。此外,Alphaproteobacteria 和 Lachnospiraceae(0.95,0.91-0.98,p<0.01;0.97,0.94-0.99,p=0.02,分别)与 PCOS 之间呈双向因果关系。
本研究从遗传角度提供了肠道微生物群与 PCOS 之间存在双向因果关系的证据。