Researchers led by the University of East Anglia performed genetic analyses on the urine and prostate tissue of more than 600 men with and without prostate cancer and found five species of bacteria linked to rapid progression of the disease.
THE study does not prove that the bacteria drive or exacerbate prostate cancer, but if work currently under way confirms their role, researchers can develop tests to identify men most at risk and potentially find antibiotics to prevent the cancer from claiming thousands of lives each year.
“This is an exciting discovery that has the potential to truly revolutionise treatment for men,” said Dr Hayley Luxton of Prostate Cancer UK, which co-funded the research.
Writing in the journal European Urology Oncology, the scientists describe how their genetic investigations found five species of bacteria – three new to science – that were associated with advanced prostate cancer. Men who had one or more of the species in their urine, prostate or tumour tissue were 2.6 times more likely to see their early stage cancer progress to advanced disease than men who did not.
Lead scientist Colin Cooper, a professor of cancer genetics at the University of East Anglia, said it was possible the bacteria are not involved in the disease. For example, men with more aggressive prostate cancer may have immune system deficiencies that allow certain bacteria to thrive. But the researchers strongly suspect the microbes are involved, just as Helicobacter pylori infections raise the risk of stomach cancer.
“If you knew for sure that a species of bacteria was causing prostate cancer, you could work out an antibiotic to remove it and that would prevent progression, one would hope,” Cooper said. But this is not as straightforward as it sounds, he cautioned. “There are many complications. Antibiotics don’t get into the prostate very well and you would need to choose an antibiotic that only kills certain bacteria.”
While prostate cancer is the most common form of the disease found in men, in many cases patients die with the disease rather than because of it. The more aggressive forms of prostate cancer claim about 12,000 lives in the UK each year.
Prof Rosalind Eeles, a cancer geneticist on the study at the Institute of Cancer Research in London, said it was a “very interesting result” to find “novel micro-organisms” in prostate cancer cases. “It is not yet known if they are causative but if this could be proven, then we have a potential route for prevention,” she said. “The way that we may be able to prove this is to see if these organisms are never found in prostate samples that have no cancer.”
Genetic information on the microbes has already allowed the scientists to piece together how they may behave in the body, including what toxins and other substances they might release. This has led them to develop half a dozen hypotheses around how the bugs could cause prostate cancer.
“We currently have no way of reliably identifying aggressive prostate cancers, and this research could help make sure men get the right treatment for them,” Luxton added.
“If the team can demonstrate that these newly identified bacteria can not only predict, but actually cause aggressive prostate cancer, for the first time we may actually be able to prevent prostate cancer occurring. This would be a huge breakthrough that could save thousands of lives each year.”
Study details
Microbiomes of Urine and the Prostate Are Linked to Human Prostate Cancer Risk Groups
Rachel Hurst, Emma Meader, Abraham Gihawi, Daniel Brewer, John Wain, Colin Cooper et al.
Published in European Urology Oncology on 18 April 2022
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.
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