Microbiomes of Urine and the Prostate Are Linked to Human Prostate Cancer Risk Groups

Abstract

Background: Bacteria play a suspected role in the development of several cancer types, and associations between the presence of particular bacteria and prostate cancer have been reported.

Objective: To provide improved characterisation of the prostate and urine microbiome and to investigate the prognostic potential of the bacteria present.

Design, setting, and participants: Microbiome profiles were interrogated in sample collections of patient urine (sediment microscopy: n = 318, 16S ribosomal amplicon sequencing: n = 46; and extracellular vesicle RNA-seq: n = 40) and cancer tissue (n = 204).

Outcome measurements and statistical analysis: Microbiomes were assessed using anaerobic culture, population-level 16S analysis, RNA-seq, and whole genome DNA sequencing.

Results and limitations: We demonstrate an association between the presence of bacteria in urine sediments and higher D'Amico risk prostate cancer (discovery, n = 215 patients, p < 0.001; validation, n = 103, p < 0.001, χ² test for trend). Characterisation of the bacterial community led to the (1) identification of four novel bacteria (Porphyromonas sp. nov., Varibaculum sp. nov., Peptoniphilus sp. nov., and Fenollaria sp. nov.) that were frequently found in patient urine, and (2) definition of a patient subgroup associated with metastasis development (p = 0.015, log-rank test). The presence of five specific anaerobic genera, which includes three of the novel isolates, was associated with cancer risk group, in urine sediment (p = 0.045, log-rank test), urine extracellular vesicles (p = 0.039), and cancer tissue (p = 0.035), with a meta-analysis hazard ratio for disease progression of 2.60 (95% confidence interval: 1.39-4.85; p = 0.003; Cox regression). A limitation is that functional links to cancer development are not yet established.

Conclusions: This study characterises prostate and urine microbiomes, and indicates that specific anaerobic bacteria genera have prognostic potential.

Patient summary: In this study, we investigated the presence of bacteria in patient urine and the prostate. We identified four novel bacteria and suggest a potential prognostic utility for the microbiome in prostate cancer.

Keywords: 16S ribosomal amplicon sequencing; Anaerobic bacteria; Cancer progression; Metagenomic sequencing; Metastases; Microbiome; Microbiota; Prognosis; Prostate cancer; Urine.