Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY Acta Obstetricia et Gynecologica Scandinavica Pub Date : 2024-09-10 DOI:10.1111/aogs.14957

Ruo-Lin Mao, Xiang-Fei Wang, Jue-Pu Zhou, Meng Wang, Rui Long, Lei Jin, Li-Xia Zhu

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Abstract

Introduction

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.

Material and Methods

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.

Results

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.

Conclusions

Our study provides evidence of the bidirectional causal association between gut microbiota and PCOS from a genetic perspective.

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肠道微生物群与多囊卵巢综合征之间的因果关系：双向孟德尔随机研究

导言以往的研究已经确定了肠道微生物群与多囊卵巢综合征（PCOS）之间的联系，但对其确切的因果关系却知之甚少。因此，本研究旨在探讨肠道微生物群与多囊卵巢综合征之间是否存在精确的因果关系。数据集来自已发表的有关肠道微生物群组成的最大规模荟萃分析和 IEU 开放全基因组关联研究项目数据库的 FinnGen 队列。使用了反方差加权（IVW）、MR-Egger、基于最大似然法的受限孟德尔随机化、加权中位数、加权模式和简单模式。结果 MR 分析共鉴定出 211 个肠道微生物群分类群。其中有 9 个细菌类群，包括阿尔法蛋白菌（0.55，0.30-0.99，p = 0.04）、芽孢杆菌（1.76，1.07-2.91，p = 0.03）、嗜双链杆菌（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）、蓝藻（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），在上述MR方法中发现至少包括IVW方法与PCOS相关。Cochran's Q 统计量和 MR-Egger 截距检验表明没有明显的异质性。此外，在反向 MR 分析中，69 个分类群至少在 IVW 方法中显示出显著性，其中 25 个具有正相关性，37 个具有负相关性。此外，Alphaproteobacteria 和 Lachnospiraceae（分别为 0.95，0.91-0.98，p <0.01；0.97，0.94-0.99，p = 0.02）与 PCOS 存在双向因果关系。

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来源期刊

Acta Obstetricia et Gynecologica Scandinavica 医学-妇产科学

CiteScore

8.00

自引率

4.70%

发文量

180

审稿时长

3-6 weeks

期刊介绍： Published monthly, Acta Obstetricia et Gynecologica Scandinavica is an international journal dedicated to providing the very latest information on the results of both clinical, basic and translational research work related to all aspects of women’s health from around the globe. The journal regularly publishes commentaries, reviews, and original articles on a wide variety of topics including: gynecology, pregnancy, birth, female urology, gynecologic oncology, fertility and reproductive biology.