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.
Citation
Hurst , R , Meader , E , Gihawi , A , Rallapalli , G , Clark , J , Kay , G L , Webb , M , Manley , K , Curley , H , Walker , H , Kumar , R , Schmidt , K , Crossman , L , Eeles , R A , Wedge , D C , Lynch , A G , Massie , C E , CRUK-ICGC Prostate Group , Yazbek-Hanna , M , Rochester , M , Mills , R D , Mithen , R F , Traka , M H , Ball , R Y , O'Grady , J , Brewer , D S , Wain , J & Cooper , C S 2022 , ' Microbiomes of urine and the prostate are linked to human prostate cancer risk groups ' , European Urology Oncology , vol. 5 , no. 4 , pp. 412-419 . https://doi.org/10.1016/j.euo.2022.03.006
Publication
European Urology Oncology
Status
Peer reviewed
ISSN
2588-9311Type
Journal article
Rights
Copyright © 2022 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Description
Funding: This work was funded by Prostate Cancer UK (research grant ref RIA15-ST2-029, MA-ETNA19-003), the Bob Champion Cancer Trust, and Big C Cancer Charity (ref 16-09R). We are grateful for and acknowledge support from the Masonic Charitable Foundation Successor to the Grand Charity, Movember, the Prostate Cancer Research Centre, the King Family, and the Stephen Hargrave Trust. We also acknowledge funding from Cancer Research UK and Dallaglio Foundation that supported the ICGC project (research grant ref. C5047/A22530). John Wain and Justin O’Grady were funded by the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent project BBS/E/F/000PR10349. Maria Traka was funded by the BBSRC Core Capability Grant BB/CCG1860/1 and its constituent project BBS/E/F/00044600 Food Databanks National Capability.Collections
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