Causal Effects between Gut Flora Significantly Associated with Cervical Cancer and 1400 Metabolites: A Mendelian Randomized Study

Background: Cervical cancer is a life-threatening disease that substantially affects human health. We investigated the association between metabolites, intestinal flora, and cervical cancer through Mendelian analysis to identify metabolic markers for the diagnosis and treatment of cervical cancer. Methods: Using data from the FinnGen Biobank, MiBioGen, and GWAS catalog, we conducted a causal study linking the gut microbiota to cervical cancer. Single nucleotide polymorphisms (SNP) information on gut flora linked to cervical cancer and 1400 metabolites underwent Mendelian analysis. We used inverse variance weighting (IVW), Mendelian Randomization (MR)-Egger, Weighted median (WM), simple mode, and weighted mode for the analysis. Sensitivity analysis included the Cochran Q test, funnel plot, “leave-one-out”, and MR-Egger intercept test. Results: Our findings identified four microbial groups with important causal associations with cervicitis: Pasteurellaceae, Veillonellaceae, Odoribacter, and Bacillales, which showed a positive correlation with cervical cancer. In addition, Pasteurellaceae were positively associated with cervical cancer. In a Mendelian analysis of 1400 blood metabolites, we confirmed 43 metabolites causally linked to Odoribacter, with 20 positively and 23 negatively correlated. Among the 38 metabolites, 27 were positively correlated, and 11 were negatively correlated with Veillonellaceae. For Pasteurellaceae, 44 metabolites were causally associated with 27 positive and 17 negative metabolites. Additionally, 21 metabolites were significantly correlated with Bacillales, with 11 positive and 10 negative correlations. The IVW estimates were significant, and the sensitivity analysis revealed no heterogeneity or pleiotropy. Conclusion: Mendelian studies provide robust evidence for the role of specific metabolites in cervical cancer, showing a causal link with the gut flora. These findings could lead to the development of new diagnostic tools and treatments. However, their clinical application remains unclear, and further research is required to confirm and optimize these ideas. Continued exploration can enhance our understanding of cervical and other cancers, aiding in their prevention and treatment.