Gut microbiota and risk of polycystic ovary syndrome: Insights from Mendelian randomization

Jing-Wei Li; Yu-Zhi Chen; Yu Zhang; Li-Hua Zeng; Kai-Wei Li; Bao-Zhen Xie; Song-Ping Luo; Jie Gao

doi:10.1016/j.heliyon.2023.e22155

Gut microbiota and risk of polycystic ovary syndrome: Insights from Mendelian randomization

Heliyon. 2023 Nov 21;9(12):e22155. doi: 10.1016/j.heliyon.2023.e22155. eCollection 2023 Dec.

Authors

Jing-Wei Li¹, Yu-Zhi Chen¹, Yu Zhang¹, Li-Hua Zeng¹, Kai-Wei Li¹, Bao-Zhen Xie¹, Song-Ping Luo², Jie Gao²

Affiliations

¹ First School of Clinical Medicine, Guangzhou University of Chinese Medicine, # No.12 Ji Chang Road, 510405, Guangzhou City, Guangdong Province, China.
² The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, 510405 Guangzhou City, Guangdong Province, China.

Abstract

Background: Polycystic ovary syndrome (PCOS) is a multifaceted endocrine and metabolic syndrome with complex origins and pathogenesis that has not yet been fully elucidated. Recently, the interconnection between gut microbiota and metabolic diseases has gained prominence in research, generating new insights into the correlation between PCOS and gut microbiota composition. However, the causal link between PCOS and gut microbiota remains relatively unexplored, indicating a crucial gap in current research.

Methods: We conducted a two-sample Mendelian randomization analysis using summary statistics obtained from the MiBioGen Consortium's extensive genome-wide association studies (GWAS) meta-analysis, focusing on the gut microbiota. Summary statistics for PCOS were acquired from the FinnGen Consortium R7 release data. Various statistical approaches, including inverse variance weighted, MR-Egger, maximum likelihood, weighted model, and weighted median, have been employed to investigate the causal association between the gut microbiota and PCOS. Additionally, we performed a reverse causal analysis. Cochran's Q statistic was used to assess the heterogeneity of the instrumental variables. Regarding the relationships between PCOS and specific genera within the gut microbiota, a significance level of P < 0.05 was observed, but only when q ≥ 0.1.

Results: Our analysis revealed that specific microbial genera, namely Bilophila (P = 4.62 × 10^-3), Blautia (P = 0.02), and Holdemania (P = 0.04), displayed a protective effect against PCOS. Conversely, the presence of the Lachnospiraceae family of bacteria was associated with a detrimental effect on PCOS (P = 0.04). Furthermore, reverse Mendelian randomization analysis confirmed the significant influence of Lachnospiraceae on PCOS. No significant variations in instrumental variables or evidence of horizontal pleiotropy were observed.

Conclusions: The results revealed a definitive causal link between PCOS and the presence of Bilophila, Blautia, Holdemania, and Lachnospiraceae in the gut microbiota. This discovery could provide pivotal insights, leading to novel preventive and therapeutic approaches for PCOS.

Keywords: Genetics; Gut microbiota; Mendelian randomization; PCOS; SNPs.