Dynamic causal effects of gut microbiota on cervical Cancer lesion progression

Abstract

Many investigations have highlighted the involvement of the intestinal microbiota in the progression of cervical cancer lesions; however, the causal link between them remains to be confirmed. We employed two-sample Mendelian randomization (MR) as a alternative to randomized controlled trials (RCTs) to explore the association between intestinal microbiota and high-risk Human Papillomavirus (HPV) infection, cervical intraepithelial neoplasia (CIN), and cervical cancer (CC). This method allowed for a detailed investigation of the underlying mechanistic interactions within the gut-cervix axis. The analysis predominantly encompassed the utilization of inverse variance weighting (IVW) and the Wald ratio test. Additionally, various sensitivity analysis methods were employed to validate the findings. We uncovered a total of 17 gut microbial taxa associated with HPV infection, 9 taxa related to CIN, and 7 taxa linked to CC. At different stages of cervical cancer lesions, various gut microbial communities play either protective or promoting roles. However, some microbial communities also act as persistent risk factors in promoting the progression of CC. Our investigation has revealed that the gut microbiota exerts a considerable impact along the entire spectrum of CC progression within the gut-cervix axis. These findings lay a foundation for prospective research focused on the utilization of gut microbiota in cervical cancer screening, prevention, and therapeutic strategies.