A team of researchers has found that the gut bacteria of people with bowel cancer are more often infected with viruses. This suggests that not only the bacteria themselves but also what lives inside them may decide how the disease develops.
When people develop bowel cancer, their gut bacteria are more likely to harbour certain viruses.
That is striking, because almost everyone carries these bacteria – without becoming ill.
A new study comparing bacteria from healthy individuals with those from people with bowel cancer suggests that not only the bacteria themselves matter but also the viruses they carry – viruses that can alter how the bacteria act.
This brings a central question into focus: is it the bacteria themselves – or what lives inside them – that drives the link to cancer?
“The paradox is that virtually 100% of people have these bacteria in their intestines, yet they are also linked to the development of bowel cancer. If we can confirm our findings, it opens the possibility that we may be able to screen for these viruses to identify people at increased risk of developing bowel cancer or use treatments targeting the viruses to reduce that risk,” says Ulrik Stenz Justesen, Professor and Consultant from the Department of Clinical Microbiology at Odense University Hospital and the University of Southern Denmark in Odense.
The research has been published in Communications Medicine.
What distinguishes the bacteria of people with and without bowel cancer?
Previously, Ulrik Stenz Justesen and colleagues found that people with bowel cancer have an overrepresentation of Bacteroides fragilis bacteria in their blood.
This indicates that these bacteria are linked with the risk of developing bowel cancer.
But this link has been difficult to explain: almost everyone carries these bacteria in their gut, yet only some develop bowel cancer – perhaps because the bacteria are not entirely the same, genetically speaking.
The team therefore set out to dig a little deeper and determine what distinguishes the bacteria of people with bowel cancer from those of healthy individuals.
To do this, they analysed the genetic material of bacteria from both groups.
“We thought that small genetic differences could explain the variation, but to investigate that, you have to work your way through vast quantities of genetic data – and this is both demanding and time-consuming,” explains Ulrik Stenz Justesen.
This data processing was carried out by Flemming Damgaard, Ulrik Stenz Justesen’s colleague and a PhD student.
Viruses – not just bacteria – set patients apart
The analysis revealed clear differences between bacteria from healthy individuals and those from people with bowel cancer.
But the researchers looked more closely and found that the differences did not lie in the bacteria themselves but in what lived inside them: two distinct viruses embedded in their genetic material – built into the bacteria’s DNA – where they can influence how the bacteria function.
Some of the bacteria of people with bowel cancer were infected with one of the viruses, and others carried both.
In bacteria from healthy individuals, by contrast, these viruses were not present at all – and with them, none of the same changes in bacterial behaviour.
“Suddenly, some of the pieces fall into place. We and others have carried out many studies of these bacteria and have not been able to explain why they are associated with the development of cancer for some people but not others. This points to the fact that it is not only about the bacteria themselves but also about the viruses they carry – and how these viruses change them,” says Ulrik Stenz Justesen.
To test the finding, the researchers also analysed bacteria from stool samples from more than 800 people with and without bowel cancer.
They found the same pattern again: the viruses within the bacteria set patients apart from healthy individuals.
Next step: do the viruses make the bacteria more harmful?
The finding raises the next question: whether it is in fact the viruses inside the bacteria that alter their function – and thereby make the difference.
Ulrik Stenz Justesen says that this is plausible but that it is still too early to say exactly how it might happen.
This is now being explored in mouse studies, in which mice that are prone to developing bowel cancer are given the bacteria in question to determine whether bacteria carrying viruses are more likely to lead to cancer than those without.
“This will bring us closer to establishing causality – in other words, whether the virus-infected bacteria are actually the cause of cancer rather than simply a by-product,” says Ulrik Stenz Justesen.
A separate project is also underway in which tumour tissue taken from patients’ intestines is being examined in more detail.
The aim is to identify virus-infected bacteria not only in stool samples but also within the tumours themselves.
New possibilities: screening – and perhaps vaccines in time
If it turns out that the viruses make the bacteria carcinogenic, it could change our understanding of what drives bowel cancer.
One possible implication is screening programmes, where people found to carry virus-infected bacteria are followed more closely through cancer screening.
It is also conceivable that vaccines could be developed against the identified viruses, preventing them from infecting the bacteria in the first place.
If that proves possible, a vaccine could potentially reduce the risk of the disease significantly.
“We are not there yet. Before we get that far, we need more data so that we can better understand both the association and any causal link. But it is clear that, in the longer term, our discovery has the potential to improve both the prevention and treatment of bowel cancer,” concludes Ulrik Stenz Justesen.
