Gut microbiota and ovarian-related diseases: insights from a Mendelian randomization study on the gut-ovary axis

This study aimed to investigate the causal associations between 119 gut microbiota traits and seven ovarian-related diseases using a bidirectional Mendelian randomization (MR) study. Publicly available genome-wide association study (GWAS) data were used to identify instrumental variables (IVs) for exposures after applying rigorous quality control criteria. This study employed a two-sample MR framework, primarily using the inverse-variance weighted (IVW) method, to investigate genetically predicted causal relationships between 119 gut microbial taxa and seven ovarian-related diseases: polycystic ovary syndrome (PCOS), primary ovarian failure (POF), endometriosis of ovary (OEM), ovarian hyperstimulation syndrome (OHSS), ovarian cyst, benign neoplasm of ovary, and malignant neoplasm of ovary. Sensitivity analyses were conducted to evaluate the robustness of the findings. Reverse MR analyses were also performed to explore potential reverse causality. MR analysis revealed that PCOS was associated with 47 single-nucleotide polymorphisms (SNPs) from four bacterial genera, POF was linked to 20 SNPs from two bacterial genera, OEM showed association with 18 SNPs from one bacterial genus, OHSS was related to 48 SNPs from four bacterial genera, ovarian cyst was connected with 31 SNPs from two bacterial genera, benign neoplasm of ovary was associated with 47 SNPs from four bacterial genera, and malignant neoplasm of ovary was linked to 61 SNPs from five bacterial genera. Sensitivity analyses confirmed the stability and reliability of these findings. The reverse MR analysis suggested bidirectional causal relationships between gut microbiota and the seven ovarian-related diseases. Our study highlights significant genetic links between gut microbiota and seven ovarian-related diseases, offering valuable insights for future mechanistic research and potential clinical applications.