Causal Relationship Between Gut Microbiota and Benign Prostatic Hyperplasia: A Two-Sample Mendelian Randomization Analyses, 16S rRNA Sequencing and Clinical Retrospective Study.

Recent studies suggest potential associations between gut microbiota (GM) and benign prostatic hyperplasia (BPH); however, the causal relationship remains uncertain. This study aims to explore the potential causal links between GM and BPH through Mendelian randomization (MR) analysis. A two-sample MR analysis was conducted using data from genome-wide association studies in accordance with the MR-STROBE statement. The inverse variance-weighted (IVW) method was utilized as the primary estimator. Robustness was evaluated by heterogeneity testing, horizontal pleiotropy assessment, and leave-one-out analyses. Fecal samples from BPH patients and healthy controls underwent 16S rRNA sequencing to evaluate their association with lower urinary tract symptom (LUTS) severity. IVW analyses associated Phascolarctobacterium (OR = 1.286; 95% CI, 1.023-1.618; p = 0.031), Faecalibacterium (OR = 1.134; 95% CI, 1.008-1.275; p = 0.037), and Escherichia-Shigella (OR = 1.348; 95% CI, 1.121-1.621; p = 0.002) with higher BPH risk, while Lactobacillus (OR = 0.572; 95% CI, 0.412-0.793; p < 0.001) and Burkholderia (OR = 0.718; 95% CI, 0.565-0.912; p = 0.007) were protective. WM and MR-Egger confirmed only Escherichia-Shigella as consistently associated. Reverse MR found no causal effect of BPH on these taxa, with no heterogeneity or pleiotropy detected. 16S rRNA sequencing showed greater Escherichia-Shigella abundance in BPH patients than controls. Multivariate analysis identified Escherichia-Shigella relative abundance as an independent predictor of severe LUTS (OR = 1.10; 95% CI, 1.01-1.21; p = 0.046). ROC analysis demonstrated its predictive value for LUTS severity (AUC = 0.777; 95% CI, 0.649-0.876; p < 0.001). Our study supports a potential causal role of GM in BPH, with Escherichia-Shigella emerging as a key predictor of LUTS severity. These findings may provide insights for future therapeutic interventions targeting microbial dynamics in BPH treatment.