Discovery of new bacteria opens fresh avenues for prostate cancer research

University of East Anglia researchers have discovered the genetic blueprints of 18 new bacterial species collected from prostate cancer patients.

Most came from the mouth, including new types of Porphyromonas, which the team has previously linked to more aggressive prostate cancer, and Treponema.

Whether they contribute to prostate cancer is unknown, but this work provides new insights into microbes in cancer patients and could uncover links that improve understanding of how cancer develops.

The discovery shows how detailed bacterial genomes can be assembled from the sequencing data left over when researchers study human DNA, at no additional cost and without collecting a single extra sample.

How the research happened

The team recovered 249 near-complete bacterial genomes from 194 prostate cancer patients. Twenty-four of these did not match any species on record.

The study is one of several major publications from the Pan Prostate Cancer Group (PPCG), a global collaboration co-founded and co-led by scientists at UEA and The Institute of Cancer Research, London.

The consortium has brought together researchers from nine countries and molecular data from more than 2,000 prostate cancers to create one of the world's most comprehensive resources for studying the disease.

In the UK, the research was co-funded by Prostate Cancer UK and Cancer Research UK, alongside funding from a range of national and international organizations supporting participating research groups worldwide.

Reading what was thrown away

When a tumor or a blood sample is sequenced, a small proportion of the reads do not match human DNA at all, so they are normally filtered out as 'noise' and discarded. In this study the UEA team kept them and used a technique called metagenomic assembly to rebuild whole bacterial genomes from the fragments, screening 2,176 sequencing datasets from the PPCG.

Now that we have the genomes of these bacteria, we can develop tests for them in clinical samples, work out how we can grow them and begin to study their genes and how they might be linked with cancer.

Every one of these organisms was hiding in plain sight. The data had already been generated, paid for and analyzed for a completely different purpose, and the bacterial sequences were sitting in the part everyone throws away.

The question was whether anything useful would survive that process, and the answer turned out to be yes. One of the newly identified species proved to be almost an exact genetic match to a previously documented bacteria, suggesting that the discovery is real and not an error in the data.

There is an enormous volume of cancer sequencing data in archives around the world, and we can use these to look for evidence of new bacteria"

Dr. Abraham Gihawi, first author of the study, UEA's Norwich Medical School

Porphyromonas, the genus that includes the principal bacterium behind gum disease, was the most frequently recovered.

The team has given formal provisional names to 16 of the new organisms, including Candidatus Porphyromonas leptis, Candidatus Treponema oralis and Candidatus Nanosyncoccus prostatocharitus.

Why this matters for patients

The role of oral bacteria in disease elsewhere in the body is well established.

For example Viridans streptococci, common in the mouth, cause around one in five cases of the heart condition infective endocarditis, while Fusobacterium nucleatum can spread with bowel tumors to the liver, where antibiotics have been shown to reduce both the bacterium and tumor growth in laboratory models.

This research is at an early stage, but evidence is emerging that men with gum disease have a slightly higher risk of developing prostate cancer, and Porphyromonas gingivalis, the main bacterium behind gum disease, has been found in both dental plaque and prostate fluid from the same patients.

In 2024, researchers reported that it may worsen benign prostate enlargement through an inflammatory mechanism they described as an "oral-prostate axis".

However, progress has been hampered because many of these microbes have never been grown in the laboratory, lack reference genomes and cannot be detected with species-specific tests, making their role difficult to study.

This study addresses that gap. As well as sequencing the genomes of the newly identified species, the UEA team predicted the conditions needed to grow them and developed a validated DNA test to detect one species with precision.

Prof Daniel Brewer, of UEA's Norwich Medical School and senior author, said: "The bacteria we recovered are overwhelmingly oral organisms. Part of that is simply that there are far more bacteria in the mouth than in prostate tissue, so they assemble more readily. But the mouth keeps turning up in prostate cancer research, and these are the organisms at the center of it.

"We reported in 2022 that men carrying a set of anaerobic bacteria, several of them from the oral cavity, were more than twice as likely to see their cancer progress. In bowel cancer, that kind of observation has already been followed through to the point where an oral bacterium is treated as a target. Prostate cancer is some way behind, and the reason is practical rather than scientific, the organisms involved had never been properly characterized.

"A biomarker is only useful if you can measure it, and you cannot measure an organism that has no genome and no test.

"Until now we could say a type of bacteria was involved, which lumps very different species together. We can now work species by species - asking whether one of them is driving aggressive disease, and whether doing anything about it changes the outcome."

Part of a wider effort

Prof Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research, London, Honorary Consultant at The Royal Marsden NHS Foundation Trust, and co-founder of the PPCG, said: "We know that prostate cancer is not one single disease. There are a range of ways that prostate cancer develops and behaves, and we need to understand the biology behind those differences in order to detect and treat the cancer correctly.

"The international team we have created has brought together an enormous amount of molecular information from more than 2,000 tumors worldwide. With these data, we have already uncovered clues that could help identify which prostate cancers are most likely to become aggressive. Today, this consortium publication has revealed an entirely new avenue for research, identifying bacteria associated with prostate cancer that could, in the future, be used to detect or to treat cancer.

"Our long-term goal is to help ensure that patients receive the right treatment at the right time, based on the biology of their individual cancer rather than a one-size-fits-all approach."

The PPCG has brought together whole genome sequencing data from more than 2,000 prostate cancers across nine countries and is publishing a series of studies that are redrawing the genetic map of the disease and what it means for how patients are managed.

Prof Cooper, Professor of Cancer Genetics at UEA's Norwich Medical School, said: "This group was built to answer why two men with the same diagnosis can have such different outcomes. Most of our answers so far have come from the tumor's own genetics, which tell us a great deal but which we cannot change.

"Bacteria are different. If an organism contributes to aggressive prostate cancer, that is something that could potentially be treated or prevented. Very little else in this disease offers that.

"We are not claiming these bacteria cause prostate cancer. We have found them, named them and built the tools to study them, which is the step that has to come before anyone can answer the causal question properly. What strikes me is that it cost nothing to do. The data existed, the organisms were in it, and nobody had looked."

Dr Hayley Luxton, Head of Research Impact at Prostate Cancer UK, said: "We still don't know for certain if bacteria can cause prostate cancer. Building on previous research Prostate Cancer UK funded that linked specific bacteria with aggressive prostate cancer, this new analytical approach from UEA has not only found bacterial DNA hidden in plain sight within the whole genome of prostate cancer patients, but will also help researchers investigate whether these bacteria contribute to aggressive prostate cancer. This is hugely exciting, as it could deepen our understanding of the disease and lead to more targeted and effective treatments for men.

"The next steps will be to isolate these bacterial strains from patient samples so their relationship to aggressive prostate cancer can be studied more closely. Prostate Cancer UK is dedicated to funding innovative research, and we're proud to have funded vital research like this to get men the treatments they need. We look forward to seeing what future discoveries will emerge from the Pan Prostate Cancer Group."

This research was conducted with the PPCG and colleagues at The Institute of Cancer Research, London, the University of Copenhagen, University of Melbourne, the Wellcome Sanger Institute, Weill Cornell Medicine, the Ontario Institute for Cancer Research and institutions across nine countries.

'Recovering anaerobic bacterial genomes in saliva, tumor and blood whole genome sequencing data from patients with prostate cancer' is published in npj Biofilms and Microbiomes.