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

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.

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

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).

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

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.

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

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.

European urology oncology. 2022 Apr 18 [Epub ahead of print]

Rachel Hurst, Emma Meader, Abraham Gihawi, Ghanasyam Rallapalli, Jeremy Clark, Gemma L Kay, Martyn Webb, Kate Manley, Helen Curley, Helen Walker, Ravi Kumar, Katarzyna Schmidt, Lisa Crossman, Rosalind A Eeles, David C Wedge, Andy G Lynch, Charlie E Massie, CRUK-ICGC Prostate Group , Marcelino Yazbek-Hanna, Mark Rochester, Robert D Mills, Richard F Mithen, Maria H Traka, Richard Y Ball, Justin O'Grady, Daniel S Brewer, John Wain, Colin S Cooper

Norwich Medical School, University of East Anglia, Norwich, Norfolk, UK., Microbiology Department, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK., Norwich Medical School, University of East Anglia, Norwich, Norfolk, UK; Quadram Institute Biosciences, Norwich, UK., Norwich Medical School, University of East Anglia, Norwich, Norfolk, UK; Department of Urology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK., Department of Urology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK., The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London and Sutton, UK., Oxford Big Data Institute, University of Oxford, Oxford, UK; University of Manchester, Manchester, UK., School of Medicine, University of St Andrews, St Andrews, UK; School of Mathematics and Statistics, University of St Andrews, St Andrews, UK., Hutchison/MRC Research Centre, Cambridge University, Cambridge, UK., The CRUK-ICGC Prostate Group, UK., Quadram Institute Biosciences, Norwich, UK; Liggins Institute, University of Auckland, Grafton, Auckland, New Zealand., Quadram Institute Biosciences, Norwich, UK., Norfolk and Waveney Cellular Pathology Service, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK., Norwich Medical School, University of East Anglia, Norwich, Norfolk, UK; Earlham Institute, Norwich Research Park Innovation Centre, Norwich, UK., Norwich Medical School, University of East Anglia, Norwich, Norfolk, UK. Electronic address: .

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