Gut microbiome, dietary habits, and prostate cancer: a two-step Mendelian randomization revealing the causal associations

Background: Recent studies suggest that diet fizzy drinks may contribute to prostate cancer (PCa) development. However, the causal effects between diet fizzy drinks and PCa and whether gut microbiota (GM) act as a mediator remain unclear. Methods: We conducted two-sample Mendelian Randomization (MR) analyses utilizing large-scale genome-wide association studies (GWAS) data from the UK Biobank, the MiBioGen consortium, and PCa-related datasets. The inverse-variance weighted (IVW) method was used to evaluate the causal effects of GM and dietary preferences on PCa risk. A mediation analysis was performed to investigate whether GM mediates the relationship between dietary factors and PCa risk. Results: Diet fizzy drink consumption was causally associated with reduced PCa risk (OR = 0.83, 95% CI: 0.70–0.99, P = 0.041) and decreased abundance of PCa-risk-related GM taxa (Negativicutes and Selenomonadales). Mediation analysis did not reveal a statistically significant mediation effect, with a mediation proportion of 16% (95% CI: − 0.06–0.37, P = 0.13). Conclusion: Consumption of diet fizzy drinks may reduce the risk of PCa, potentially through modulation of the GM; however, further studies are required to confirm these findings and clarify underlying mechanisms. © The Author(s) 2025.