Associations between gut microbiota and gynecological cancers: A bi-directional two-sample Mendelian randomization study

Growing evidence has suggested that gut microbiota is associated with gynecologic cancers. However, whether there is a causal relationship between these associations remains to be determined. A two-sample Mendelian randomization (MR) evaluation was carried out to investigate the mechanism associating gut microbiota and 3 prevalent gynecological cancers, ovarian cancer (OC), endometrial cancer, and cervical cancer as well as their subtypes in individuals of European ancestry. The Genome-wide association studies statistics, which are publically accessible, were used. Eligible instrumental single nucleotide polymorphisms that were significantly related to the gut microbiota were selected. Multiple MR analysis approaches were carried out, including inverse variance weighted, MR-Egger, Weighted Median methods, and a range of sensitivity analyses. Lastly, we undertook a reverse MR analysis to evaluate the potential of reverse causality. We sifted through 196 bacterial taxa and identified 33 suggestive causal relationships between genetic liability in the gut microbiota and gynecological cancers. We found that 11 of these genera could be pathogenic risk factors for gynecological cancers, while 19 could lessen the risk of cancer. In the other direction, gynecological cancers altered gut microbiota composition. Our MR analysis revealed that the gut microbiota was causally associated with OC, endometrial cancer, and cervical cancer. This may assist in providing new insights for further mechanistic and clinical studies of microbiota-mediated gynecological cancer.