Gut microbiota and risk of cervical cancer: a Mendelian multivariable randomization study.

Background and hypothesis: Epidemiological evidence demonstrates associations between gut microbial dysbiosis and cervical cancer, though causal inference remains limited by potential confounding.

Study design: A meta-analysis of the largest available genome-wide association study (GWAS) meta-analysis using the MiBioGen consortium (n = 14,306 individuals; 8,107,040 SNPs analyzed) was conducted for the summary statistics of the gut microbiome. A two-sample Mendelian randomization study was performed using the statistics of cervical cancer from BioBank Japan (BBJ) and the European Bioinformatics Institute (EBI) GWAS Catalog. The causal relationship between the gut microbiome and cervical cancer was examined using inverse variance weighting, maximum likelihood, MR-Egger, weighted median, weighted model, and MR-PRESSO methods. The Cochran Q statistic was used to quantify the heterogeneity of the instrumental variables.

Study results: The odds ratio (OR) values obtained by the IVW method indicate that the consistent microbial communities in the validation results from two different cervical cancer datasets are: Actinomyces (BBJ OR = 0.52, 95% CI: 0.29-0.92, P < 0.05), (EBI OR = 0.55, 95% CI: 0.29-0.87, P < 0.05) It has a protective effect on the occurrence of cervical cancer, Lachnospiraceae UCG001 (BBJ OR = 2.00, 95% CI: 1.11-3.58, P < 0.05), ( EBI OR = 1.91, 95% CI: 1.16-3.13, P < 0.05) It has a promoting risk effect on the occurrence of cervical cancer, and there is no significant heterogeneity or horizontal pleiotropy.

Conclusions: Both datasets consistently showed that Actinomyces was protective against cervical cancer (BBJ OR = 0.52; EBI OR = 0.55), while Lachnospiraceae UCG001 increased risk (BBJ OR = 2.00; EBI OR = 1.91), with no evidence of heterogeneity or pleiotropy in these robust MR analyses.