Causal Relationship Between Gut Microbiota and Gynecological Tumor:A Two-Sample Mendelian Randomization Study

Abstract

Abstract Background: Previous research has linked alterations in the composition of the gut microbiota to a variety of gynecologic tumors.Nevertheless, although the causal relationship between the gut microbiota and gynecologic tumors remains to be fully elucidated. Therefore, this study uses a two-sample Mendelian randomization analysis (MR) to explore the causal correlation between the gut microbiota community and prevalent gynecologic tumours. With the goal of identifying specific pathogenic bacterial communities that may be involved in gynecologic tumor development. Materials and Methods: We utilized data from the MiBioGen consortium’s Genome-Wide Association Study (GWAS) on gut microbiota as the exposure variable. Four common gynecologic neoplasms including uterine fibroids (UF), endometrial cancer (EC), ovarian cancer (OC) and cervical cancer (CC) were selected as the outcome variables. Single-nucleotide polymorphisms (SNPs) significantly associated with exposure were selected as the instrumental variables (IVs). The inverse variance-weighted (IVW) method was used as the principal MR analysis to assess the causal relationship between gut microbiota and these tumors, with the goal of identifying microbial communities associated with gynecologic tumor development. An independent validation cohort was used for further validation. We conducted sensitivity analyses to ensure robustness of the findings. Lastly, we performed reverse MR analysis to assess the potential for reverse causation. Results: Combining the results from the discovery and validation cohorts, we found that higher relative abundance of Lachnospiraceae is associated with lower risk of UF (OR: 0.882, 95% CI: 0.793-0.999, P = 0.982). Conversely, a higher incidence of OC is associated with a higher relative abundance of Lachnospiraceae (OR: 1.329, 95% CI: 1.019-1.732, P= 0.036). Sensitivity analyses confirmed the reliability of these results. Furthermore, the results of the reverse MR analysis showed no evidence of a reverse cause-and-effect relationship between UF, OC, and Lachnospiraceae. Conclusion: In this study, a causal relationship between Lachnospiraceae and both UF and OC was established. This provides new insights into the role of gut microbiota in the mechanism of gynecological tumor development.