Min Qiusi, Geng Hongling, Gao Qian, Xu Min
Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China.
Front Microbiol. 2023 Jul 24;14:1203902. doi: 10.3389/fmicb.2023.1203902. eCollection 2023.
Increasing evidence from observational studies and clinical experimentation has indicated a link between the gut microbiotas (GMs) and polycystic ovary syndrome (PCOS), however, the causality and direction of causality between gut microbiome and PCOS remains to be established.
We conducted a comprehensive search of four databases-PubMed, Cochrane Library, Web of Science, and Embase up until June 1, 2023, and subjected the results to a meta-analysis. In this study, a bidirectional two-sample Mendelian randomization (MR) analysis was employed to investigate the impact of gut microbiota on polycystic ovary syndrome (PCOS). The genome-wide association study (GWAS) data for PCOS comprised 113,238 samples, while the GWAS data for gut microbiota were derived from the MiBioGen consortium, encompassing a total sample size of 18,340 individuals. As the largest dataset of its kind, this study represents the most comprehensive genome-wide meta-analysis concerning gut microbiota composition to date. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables at various taxonomic levels, including Phylum, Class, Order, Family, and Genus. The causal associations between exposures and outcomes were assessed using four established MR methods. To correct for multiple testing, the false discovery rate (FDR) method was applied. The reliability and potential biases of the results were evaluated through sensitivity analysis and F-statistics.
The meta-analysis incorporated a total of 20 studies that met the criteria, revealing a close association between PCOS and specific gut microbiota species. As per the results from our MR analysis, we identified six causal associations between the gut microbiome and polycystic ovary syndrome (PCOS). At the genus level, (OR = 1.369, = 0.040), (OR = 1.548, = 0.027), and (OR = 1.488, = 0.028) were identified as risk factors for PCOS. Conversely, (OR = 0.723, = 0.040), (OR = 0.580, = 0.032), and (OR = 0.732, = 0.030) were found to be protective factors against PCOS. Furthermore, the MR-PRESSO global test and MR-Egger regression indicated that our study results were not affected by horizontal pleiotropy ( > 0.05). Finally, the leave-one-out analysis corroborated the robustness of the MR findings.
Both our meta-analysis and MR study indicates that there is a causal relationship between the gut microbiome and PCOS, which may contribute to providing novel insights for the development of new preventive and therapeutic strategies for PCOS.
观察性研究和临床实验越来越多的证据表明肠道微生物群（GMs）与多囊卵巢综合征（PCOS）之间存在联系，然而，肠道微生物群与PCOS之间的因果关系及因果方向仍有待确定。
我们对四个数据库——PubMed、Cochrane图书馆、Web of Science和Embase进行了全面检索，直至2023年6月1日，并对结果进行了荟萃分析。在本研究中，采用双向两样本孟德尔随机化（MR）分析来研究肠道微生物群对多囊卵巢综合征（PCOS）的影响。PCOS的全基因组关联研究（GWAS）数据包括113238个样本，而肠道微生物群的GWAS数据来自MiBioGen联盟，总样本量为18340人。作为同类中最大的数据集，本研究代表了迄今为止关于肠道微生物群组成最全面的全基因组荟萃分析。单核苷酸多态性（SNPs）在不同分类水平上被选作工具变量，包括门、纲、目、科和属。使用四种既定的MR方法评估暴露与结局之间的因果关联。为校正多重检验，应用了错误发现率（FDR）方法。通过敏感性分析和F统计量评估结果 的可靠性和潜在偏差。
荟萃分析共纳入20项符合标准的研究，揭示了PCOS与特定肠道微生物群物种之间的密切关联。根据我们的MR分析结果，我们确定了肠道微生物群与多囊卵巢综合征（PCOS）之间的六种因果关联。在属水平上，（比值比=1.369，P=0.040）、（比值比=1.548，P=0.027）和（比值比=1.488，P=0.028）被确定为PCOS的危险因素。相反，（比值比=0.723，P=0.040）、（比值比=0.580，P=0.032）和（比值比=0.732，P=0.030）被发现是预防PCOS的保护因素。此外，MR-PRESSO全局检验和MR-Egger回归表明我们的研究结果不受水平多效性影响（P>0.05）。最后，留一法分析证实了MR结果的稳健性。
我们的荟萃分析和MR研究均表明肠道微生物群与PCOS之间存在因果关系，这可能有助于为PCOS新的预防和治疗策略的开发提供新的见解。
