Presented by: Aaron Miller PhD
Cleveland Clinic

Introduction

Though benign prostatic hyperplasia (BPH) affects an estimated 70% of men between the ages of 60-69, the etiology is not well understood. Recently, the human urinary tract microbiome has been associated with a variety of urologic diseases, especially those mediated by an inflammatory pathway.  Here, we sought to determine associations between age-independent prostate size and microbiome.

Materials

Men over 18 years old undergoing Holmium Laser Enucleation of the Prostate (HoLEP) for BPH were recruited if they had no history of prostate cancer, prostate surgery, or pelvic radiation. Patients were excluded if they had a positive preprocedural urine culture, recent UTI requiring antibiotics, bladder stones, or if they were catheter-dependent due to obstruction. Prostate tissue samples, catheterized urine, and urethral and specimen container swabs were collected from each patient. All non-prostate samples were used as contamination controls. Patient data such as age, prostate-specific antigen (PSA) level, BPH symptoms, and prostate size were recorded. All samples underwent DNA extraction, 16S sequencing, and analysis in R statistical software. After quality control, reads associated with the controls were removed. High-quality, decontaminated data were assessed for diversity (alpha, beta, taxonomy). The correlation between amplicon sequence variants (ASVs) and patient metrics were quantified through Sparcc correlations, which was designed for count matrix correlations.

Results

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20 patients qualified, consented, and were analyzed in this study. Mean age, PSA, and prostate size were 68.6 years, 3.4 ng/mL, and 107.9 g, respectively. After bioinformatic decontamination of samples with the negative controls, diversity analyses identified distinct microbiomes: site-specific differences between the urine, urethral swab, and prostate microbiomes were greater than inter-individual variability. Common uropathogens were positively associated with prostate size.  These included five ASVs belonging to Enterobacter cloaceae (p=0.02-0.03), four Planococcaceae ASVs (p=0.008-0.03), and four Acinetobacter (p=0.014-0.026). Only one ASV in the Ralstonia genus exhibited a significant association with age (p=0.015).

Conclusion

This study is the first to characterize the prostatic microbiome in BPH and to link prostate size to specific common bacterial uropathogens, while controlling for age and contamination. Further research with a larger sample size and culturomics will provide insight into the mechanisms of how the prostate microbiome contributes to enlarged size.

Funding

Endourological Society Summer Student Scholarship

Lead Authors

Alec Sun, BS
Case Western Reserve University School of Medicine

Co-Authors

Prajit Khooblall, MD
Cleveland Clinic

Juan Sebastián Rodriquez Alvarez, MD
Cleveland Clinic

Smita De, MD, PhD
Cleveland Clinic