Arch Esp Urol. 2026 Apr;79(3):431-439. doi: 10.56434/j.arch.esp.urol.20267903.51.
ABSTRACT
BACKGROUND: Gut microbiota (GM) has been increasingly implicated in cancer development through immune modulation, metabolic regulation, and systemic inflammatory pathways. Although observational studies have suggested a potential link between GM dysbiosis and bladder cancer (BC), these findings remain susceptible to confounding and reverse causation. To our knowledge, few studies have applied a Mendelian randomisation (MR) framework to systematically evaluate the gut-bladder axis from a genetic perspective.
METHODS: We performed a two-sample MR analysis to examine associations between genetically predicted GM composition and BC risk. Genetic instruments for 119 GM taxa were obtained from the MiBioGen consortium. Summary-level genetic association data for BC were derived from the UK Biobank. The inverse variance weighted (IVW) method was used as the primary analytical approach, complemented by Mendelian randomisation-Egger regression (MR-Egger) and weighted median methods. Sensitivity analyses were conducted to assess heterogeneity and horizontal pleiotropy. Instrumental variants were further mapped to host genes to perform exploratory functional annotation and pathway enrichment analyses.
RESULTS: In the primary IVW analysis, five GM taxa demonstrated nominal associations with BC risk. Higher genetically predicted abundance of Oscillibacter (OR = 0.706, 95% CI: 0.564-0.883) and Oscillospira (OR = 0.668, 95% CI: 0.490-0.910) was associated with lower risk, whereas Lachnospiraceae (FCS020 group) was associated with increased risk (OR = 1.406, 95% CI: 1.070-1.847). However, none of the associations remained statistically significant after Bonferroni correction for multiple testing. Sensitivity analyses revealed no evidence of significant heterogeneity or directional pleiotropy, and estimates were broadly consistent across MR methods.
CONCLUSIONS: In this MR study, we identified nominal associations between genetically predicted GM composition and BC risk. As none of the findings remained statistically significant after correction for multiple testing, these results should be interpreted with caution. Further replication in independent cohorts and mechanistic investigations into the role of candidate taxa are warranted to clarify the potential involvement of the gut-bladder axis in bladder carcinogenesis.
PMID:42104697 | DOI:10.56434/j.arch.esp.urol.20267903.51
