Microbiomes of urine and the prostate are linked to human prostate cancer risk groups

Hurst, Rachel, Meader, Emma, Gihawi, Abraham, Rallapalli, Ghanasyam, Clark, Jeremy, Kay, Gemma L., Webb, Martyn, Manley, Kate, Curley, Helen, Walker, Helen, Kumar, Ravi, Schmidt, Katarzyna, Crossman, Lisa, Eeles, Rosalind A., Wedge, David C., Lynch, Andy G., Massie, Charlie E., Yazbek-Hanna, Marcelino, Rochester, Mark, Mills, Robert D., Mithen, Richard F., Traka, Maria H., Ball, Richard Y., O'Grady, Justin, Brewer, Daniel S., Wain, John and Cooper, Colin S. (2022) Microbiomes of urine and the prostate are linked to human prostate cancer risk groups. European Urology Oncology. ISSN 2588-9311

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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.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 21 Apr 2022 09:30
Last Modified: 24 May 2022 14:55
URI: https://ueaeprints.uea.ac.uk/id/eprint/84709
DOI: 10.1016/j.euo.2022.03.006

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