Thank you. Listen to this article using the player above. ✖
Want to listen to this article for FREE?
Complete the form below to unlock access to ALL audio articles.
Prostate cancer is one of the most common cancers affecting men worldwide, yet diagnosing its aggressiveness remains a major clinical challenge. Current tools, such as PSA blood tests and biopsies, often fall short in telling doctors which cancers are dangerous and which are slow-growing or unlikely to cause harm. This uncertainty can lead to overtreatment – or worse, missed opportunities for early intervention.
Now, researchers at the University of East Anglia (UEA) are investigating an unlikely new diagnostic ally: bacteria. Dr. Seshadhri Subramanian, a PhD researcher in cancer genomics at UEA, is exploring how specific bacterial species found in urine and prostate tissue could help predict the severity of prostate cancer. We spoke to him about his and his colleagues’ findings, how close we are to clinical application and what this research could mean for the future of prostate cancer care.
What sparked your interest in exploring the relationship between bacteria and prostate cancer specifically?
Seshadhri Subramanian, MD (SS):
Microbial organisms make up a large portion of living cells in the human body and are involved in various processes that are essential to human survival. Due to the vastness of their population, it seemed likely that some could be linked to disease.
Given prostate cancer’s burden and the abundance of bacteria in and around us, it felt like a natural progression to explore the link.
Can you summarize the key findings from your research at UEA regarding bacterial markers and aggressive prostate cancer?
Groundbreaking research has uncovered a significant link between specific bacteria – found in urine and the prostate – and a man’s risk of having more aggressive prostate cancer. This opens up exciting new possibilities for predicting how serious a patient’s prostate cancer might be, helping doctors make better treatment decisions.
Here’s a breakdown of the main findings:
1. Bacteria in urine linked to higher-risk prostate cancer:
The research involved looking at urine samples before prostate biopsies and examining cancer tissue itself. The study found a strong connection: men with certain bacteria present in their urine were much more likely to have a higher-risk form of prostate cancer. This discovery was consistent across a large number of patients.
2. Discovery of four brand new bacterial species:
During their investigation, the team identified four bacterial species that had never been seen before – Porphyromonas sp. nov., Varibaculum sp. nov., Peptoniphilus sp. nov. and Fenollaria sp. nov. These new species were commonly found in patient urine, and some were also detected in prostate tissue and secretions. This supports the idea of a ‘prostate-urine reflux loop,’ meaning bacteria can move between the prostate gland and the urinary tract.
3. Identifying a ‘bacterial warning sign’ for aggressive cancer:
The researchers pinpointed a specific group of five anaerobic bacteria, including three of the newly discovered species, which they named the Anaerobic Bacteria Biomarker Set (ABBS)
The presence of these ABBS bacteria was linked to a higher chance of cancer spreading. Critically, detecting ABBS bacteria in urine or prostate tissue was strongly associated with a quicker progression of prostate cancer after treatment, indicating a poorer prognosis.
A combined analysis of different sample types showed that if these bacteria were present, the risk of disease progression was 2.6 times higher.
This means that testing for these specific bacteria in urine could potentially become a new way to predict if a man’s prostate cancer is likely to be aggressive or return after initial treatment.
4. Potential ways these bacteria might influence cancer:
While the study doesn’t yet prove that these bacteria cause cancer, it offers clues about how they might contribute to its development or progression. The researchers found that these ABBS bacteria have genes involved in processes that could support cancer growth, such as:
a. Testosterone precursors: Converting cholesterol into androstenedione, a building block for testosterone, which prostate cancer needs to grow.
b. Citrate levels: Influencing citrate, a substance known to be reduced in aggressive prostate cancer.
c. Metabolic impact: Affecting other metabolic pathways in the body that cancer cells might exploit.
The findings also hint that the importance of these ABBS bacteria might extend to other types of cancer, not just prostate cancer. Future research will focus on whether these bacteria cause cancer and how we might develop new treatments to target them.
How early can these bacterial markers be detected compared to current diagnostic tools such as PSA testing or biopsies?
Researchers are looking into this area; however, at this point in time, there is no definitive answer.
This is primarily because, before we jump the gun and compare them to current gold standards of diagnosis, we need to verify that these bacteria are present in the urine for a long time before disease progression and that they are strongly associated with the subset of patients that eventually progress.
Could these bacterial markers be used to distinguish between aggressive and non-aggressive prostate cancer?
That remains the aim of this research. Right now, prostate cancer diagnosis is reliant on methods that cannot accurately distinguish or predict, at the point of diagnosis, cancers that are going to remain indolent vs those that are going to progress to a more aggressive form, requiring more intensive treatment.
This results in some patients being overtreated for a cancer that may not have affected them as much, potentially harming their quality of life.
The goal is to minimise patient suffering – both from the disease and from unnecessary treatment – and the more accurate our methods of prognostication are, the better it would be.
There is promise in this, but this method needs further validation before it can have clinical implications.
Is there a known mechanism through which the bacteria might influence cancer development?
We are investigating how the bacteria interact with the tumour, and what genes and pathways are important to that process.
Some of the methods that we think could be involved include things such as cell signaling pathways, methionine metabolism (exogenous methionine is essential to a cancer cell’s survival) and testosterone pathways.
What are the next steps in your research?
We want to find out how these bacteria interact with tumors because this could open up potential therapeutic avenues and decipher the mechanisms that bacteria use to affect tumor progression.
The ABBS list is not a final list and there may be other bacteria out there that could potentially have an association with different prognostic outcomes. Determining these bacteria could also give a more complete picture.
We also plan to determine the viability of antibiotic treatment for certain subsets of prostate cancer.
Determining if the urine is reflective of what is going on in the prostate, from a microbial point of view, would also help in reducing the patient burden.
A screen or prognostic tool that relies on the urine would be a lot less stressful on the patient compared to anything more invasive.
The research is still very much in the early stages and there are a lot of exciting questions that need to be answered about this as well.
I think it will still be a while before we see this in a clinical setting and making a meaningful impact. Studies need to be undertaken to determine the viability of this as a cost-effective method of evaluating prostate cancer patients at diagnosis.