Causal effect of gut microbiota on the risk of prostatitis: a two-sample Mendelian randomization study

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BACKGROUND: Recent studies demonstrated that chronic prostatitis (CP) is closely related to the gut microbiota (GM). Nevertheless, the causal relationship between GM and CP has not been fully elucidated. Therefore, the two-sample Mendelian randomization (MR) analysis was employed to investigate this association. METHODS: The summary data of gut microbiota derived from a genome-wide association study (GWAS) involving 18,340 individuals in the MiBioGen study served as the exposure, and the corresponding summary statistics for CP risk, representing the outcome, were obtained from the FinnGen databases (R9). The causal effects between GM and CP were estimated using the inverse-variance weighted (IVW) method supplemented with MR-Egger, weighted median, weighted mode, and simple mode methods. Additionally, the false discovery rate (FDR) correction was performed to adjust results. The detection and quantification of heterogeneity and pleiotropy were accomplished through the MR pleiotropy residual sum and outlier method, Cochran's Q statistics, and MR-Egger regression. RESULTS: The IVW estimates indicated that a total of 11 GM taxa were related to the risk of CP. Seven of them was correlated with an increased risk of CP, while the remained linked with a decreased risk of CP. However, only Methanobacteria (OR 0.86; 95% CI 0.74-0.99), Methanobacteriales (OR 0.86; 95% CI 0.74-0.99), NB1n (OR 1.16; 95% CI 1.16-1.34), Methanobacteriaceae (OR 0.86; 95% CI 0.74-0.99), Odoribactergenus Odoribacter (OR 1.43; 95% CI 1.05-1.94), and Sutterellagenus Sutterella (OR 1.33; 95% CI 1.01-1.76) still maintain significant association with CP after FDR correction. Consistent directional effects for all analyses were observed in the supplementary methods. Subsequently, sensitivity analyses indicated the absence of heterogeneity, directional pleiotropy, or outliers concerning the causal effect of specific gut microbiota on CP (p > 0.05). CONCLUSION: Our study demonstrated a gut microbiota-prostate axis, offering crucial data supporting the promising use of the GM as a candidate target for CP prevention, diagnosis, and treatment. There is a necessity for randomized controlled trials to validate the protective effect of the linked GM against the risk of CP, and to further investigate the underlying mechanisms involved.

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