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

## TL;DR

This study finds a potential causal link between gut microbiota and benign prostatic hyperplasia, with Escherichia–Shigella being a key predictor of symptom severity.

## Contribution

The study establishes a causal relationship between gut microbiota and BPH using Mendelian randomization and 16S rRNA sequencing.

## Key findings

- Escherichia–Shigella is consistently associated with higher BPH risk and LUTS severity.
- Lactobacillus and Burkholderia are protective against BPH.
- Escherichia–Shigella abundance is an independent predictor of severe LUTS.

## Abstract

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.

Our study supports a potential causal role of gut microbiota in benign prostatic hyperplasia, with Escherichia–Shigella emerging as a key contributor and predictor of lower urinary tract symptom severity. These findings may provide insights for future therapeutic interventions targeting microbial dynamics in the treatment of benign prostatic hyperplasia.