Association between gut microbiota and benign prostatic hyperplasia: a two-sample mendelian randomization study

Abstract

Background: Recent researches have shown a correlation between the gut microbiota (GM) and various diseases. However, it remains uncertain whether the relationship between GM and benign prostatic hyperplasia (BPH) is causal.

Methods: We carried out a two-sample Mendelian randomization (MR) analysis, utilizing data from the most extensive GM-focused genome-wide association study by the MiBioGen consortium, with a sample size of 13,266. Data for BPH, encompassing 26,358 cases and 110,070 controls, were obtained from the R8 release of the FinnGen consortium. We employed multiple techniques, such as inverse variance weighted (IVW), constrained maximum likelihood and model averaging methods, maximum likelihood, MR-Pleiotropy RESidual Sum and Outlier (MRPRESSO),MR-Egger, and weighted median methods, to investigate the causal relationship between GM and BPH. To evaluate the heterogeneity among the instrumental variables, Cochran's Q statistics were employed. Additionally, the presence of horizontal pleiotropy was assessed through the application of both MR-Egger and MR-PRESSO tests. The direction of causality was scrutinized for robustness using the MR-Steiger directionality test. A reverse MR analysis examined the GM previously linked to BPH through a causal relationship in the forward MR assessment.

Results: According to the analysis conducted using IVW,Eisenbergiella (odds ratio [OR]=0.92, 95% confidence interval [CI]: 0.85-0.99,P=0.022) and Ruminococcaceae (UCG009) (OR=0.88, 95% CI: 0.79-0.99, P=0.027) were found to reduce the risk of BPH, while Escherichia shigella (OR=1.19, 95% CI: 1.05-1.36, P=0.0082) appeared to increase it. The subsequent reverse MR analysis revealed that the three GM were not significantly influenced by BPH, and there was no noticeable heterogeneity or horizontal pleiotropy among the instrumental variables.Conclusion: These results indicated a causal relationship between Eisenbergiella, Ruminococcaceae (UCG009), and Escherichia shigella and BPH. Further randomized controlled trials are needed to explore more comprehensively the roles and operational mechanisms of these GM in relation to BPH.

Keywords: benign prostate hyperplasia; causal inference; genome wide association study; gut microbiota; mendelian randomization study.