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Causal association between gut microbiome and polycystic ovary syndrome: A bidirectional Mendelian randomization study

Dongqin Xia(1), Linjie Xu(2), Xi Cheng(3), Chenglu Li(4), Siyi Chen(5), Yuquan Zhang(6),


(1) Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China. Rugao Maternity Hospital, Rugao 226500, Jiangsu, China
(2) Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China
(3) Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China
(4) Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China
(5) Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China
(6) Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China
Corresponding Author

Abstract


Through implementing a bidirectional Mendelian randomization (MR) study, the causal effects between gut microbiome and polycystic ovary syndrome (PCOS) were analyzed. Summary statistics for PCOS were acquired from the FinnGen consortium R8 release data, which included 27,943 cases and 162,936 controls. The inverse-variance weighting (IVW) method was adopted for analysis. Additionally, the causality involving exposure plus the outcome was evaluated by means of MR-Egger, weighted median, simple mode methods, as well as weighted mode. The IVW estimate showed that the genera Streptococcus plus Enterorhabdus served as protectors of PCOS. By contrast, the phylum Tenericutes, genera Anaerofilum, Coprococcus 2, Lachnospiraceae ND3007 group and Ruminiclostridium 5 were identified as risk elements of PCOS. Based on reverse MR analyses from PCOS on the intestinal microbiome based on the IVW method, the phyla Tenericutes, Actinobacteria, class Actinobacteria, genera Ruminococcaceae UCG004 and Christensenellaceae R 7group exhibited a down-regulation effect after PCOS onset. The genera Bacteroides, Barnesiella, Erysipelotrichaceae UCG003, Ruminococcus gnavus group, and Veillonella were up-regulated. No horizontal pleiotropy or significant IV heterogeneity was observed. We conclude that there is a causality relationship between gut microbiome and PCOS, where some bacterial taxa can be used as biomarkers to promote targeted diagnosis and therapy for PCOS.

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