Gut microbiota and risk of ovarian diseases: a two-sample Mendelian randomization study

Abstract Background Previous studies have reported an association between gut microbial dysbiosis and ovarian diseases, however, it is not clear whether a causal association exists. Methods Two-sample Mendelian randomization (MR) analysis was performed to genetically predict the causal effects of the gut microbiota on polycystic ovary syndrome (PCOS), premature ovarian failure (POF), ovarian endometriosis, and malignant and benign ovarian neoplasms. The inverse variance weighted (IVW) method was used as the primary statistical method. A series of sensitivity analyses, including weighted median, MR-Egger, simple mode, weighted mode methods, MR pleiotropy residual sum and outlier (MR-PRESSO) and leave-one-out analysis, were also conducted to assess the robustness of the MR analysis results. Reverse MR analysis was implemented to explore whether ovarian diseases have any causal impact on the bacterial genera. Additionally, the Cochran’s Q test was used to evaluate heterogeneity among instrumental variables. Results IVW analysis revealed that several bacteria were associated with decreased risk of PCOS, POF, ovarian endometriosis, and benign and malignant ovarian neoplasm. Moreover, several bacteria were the causes of increased risks for POF, ovarian endometriosis, and benign and malignant ovarian neoplasm, respectively. Reverse MR analysis did not reveal a significant causal effect of these ovarian diseases on the gut microbiota. These findings were robust according to extensive sensitivity analyses. Conclusion Our results provide genetic evidence to support the causal relationship between specific gut microbiota taxa and ovarian diseases; thus, the gut microbiota should be considered a preventative strategy for ovarian diseases.