Hidden virus in your gut may be linked to colon cancer

In recent years, scientists have increasingly focused on the gut microbiome, the vast ecosystem of bacteria, viruses, and other microorganisms living in the digestive system.

Now, researchers from the University of Southern Denmark and Odense University Hospital have identified a previously unknown virus inside a common gut bacterium. This virus appears more often in people with colorectal cancer, offering a new clue about how the disease may develop.

A Common Gut Bacterium With a Longstanding Mystery

For years, researchers have linked one specific bacterium, Bacteroides fragilis, to colorectal cancer. However, this connection has been difficult to explain because the same bacterium is also found in most healthy individuals.

“It has been a paradox that we repeatedly find the same bacterium in connection with colorectal cancer, while at the same time it is a completely normal part of the gut in healthy people,” says Flemming Damgaard, medical doctor and PhD at the Department of Clinical Microbiology at Odense University Hospital and the University of Southern Denmark.

To resolve this contradiction, the team investigated whether there might be important differences within the bacterium itself.

They found that there were.

Discovery of a Virus Inside Gut Bacteria

The key difference turned out to be a virus living inside the bacterium. In patients who later developed colorectal cancer, Bacteroides fragilis was much more likely to carry a specific bacteriophage, a virus that infects bacteria.

“We have discovered a virus that has not previously been described and which appears to be closely linked to the bacteria we find in patients with colorectal cancer,” says Flemming Damgaard.

The researchers believe this virus represents entirely new types that have not been identified before.

“It is not just the bacterium itself that seems interesting. It is the bacterium in interaction with the virus it carries,” he explains.

Although the study shows a strong statistical link between the virus and colorectal cancer, it does not prove that the virus causes the disease.

“We do not yet know whether the virus is a contributing cause, or whether it is simply a sign that something else in the gut has changed,” says Flemming Damgaard.

Large-Scale Data Reveals a Clear Pattern

The discovery began with data from a large Danish population study involving about two million people. Researchers focused on patients who had experienced serious bloodstream infections caused by Bacteroides fragilis. A small portion of these individuals were diagnosed with colorectal cancer within weeks.

By comparing bacterial samples from patients with and without cancer, the team identified a clear pattern. Bacteria from cancer patients were more likely to contain specific viruses.

The initial findings came from a relatively small group of Danish samples, but they provided a strong starting point for further investigation.

“It was in our Danish material that we first detected a signal. That gave us a concrete hypothesis, which we were then able to investigate in larger datasets,” says Flemming Damgaard.

Confirmed Across Nearly 900 Patients Worldwide

To test whether the pattern held up globally, the researchers analyzed stool samples from 877 individuals across Europe, the United States, and Asia.

The results were consistent. People with colorectal cancer were about twice as likely to carry these viruses in their gut.

“It was important for us to examine whether the association could be reproduced in completely independent data. And it could,” says Flemming Damgaard.

While this strengthens the link, it still does not show that the virus directly causes cancer.

A New Way to Look at Cancer Risk

Up to 80 per cent of colorectal cancer risk is thought to be influenced by environmental factors, including the microorganisms in the gut.

The gut microbiome is incredibly complex, containing thousands of bacterial species and even more genetic variation. This complexity has made it difficult to pinpoint what separates healthy individuals from those who develop disease.

“The number and diversity of bacteria in the gut is enormous. Previously, it has been like looking for a needle in a haystack. Instead, we have investigated whether something inside the bacteria — namely viruses — might help explain the difference,” says Flemming Damgaard.

If the virus changes how the bacterium behaves, it could alter the gut environment in ways that influence cancer risk. This possibility is now being explored.

“We do not yet know why the virus is present, but we are investigating whether it contributes to the development of colorectal cancer,” he says.

Could This Lead to New Screening Tests?

Currently, colorectal cancer screening often involves stool tests that look for hidden blood.

In the future, researchers believe it may be possible to screen for these newly identified viruses as well.

“In the short term, we can investigate whether the virus can be used to identify individuals at increased risk,” says Flemming Damgaard.

Early analyses suggest that certain viral markers could identify about 40 per cent of cancer cases, while most healthy individuals do not carry them.

However, the researchers stress that this work is still in its early stages. More studies are needed before it could be used in clinical practice.

Fact box: Key terms

Bacteroides fragilis

A common gut bacterium found in most healthy individuals. It has previously been linked to colorectal cancer, but is also present in people without disease.

Viruses in bacteria (bacteriophages)

Some viruses live inside bacteria. They can influence the bacterium’s properties and, in some cases, alter its behavior.

Microbiome

The collective term for all microorganisms — including bacteria, viruses and fungi — that live in and on the body.

Three questions for Flemming Damgaard about the study

What did you investigate?

We investigated how gut bacteria may contribute to the development of colorectal cancer.

What is the most important finding?

We discovered a new and previously undescribed virus that infects gut bacteria in patients with colorectal cancer.

How could the results be used?

In the longer term, it may become possible to test for these viruses in stool samples to assess the risk of colorectal cancer and potentially improve prevention and treatment.

Fact box: Ongoing research projects

Flemming Damgaard and his research colleagues are continuing their work in three separate projects:

• We are cultivating Bacteroides fragilis carrying the virus in an artificial gut model to examine how gut tissue, virus and bacterium interact. The project is funded by the Louis Hansen Foundation.
• We are about to inoculate colorectal cancer tumors and look for the bacterium and the virus directly within tumor tissue. This project is funded by the Novo Nordisk Foundation.
• We will test in mice that are genetically predisposed to develop cancer whether they develop the disease more rapidly if they carry the bacterium with the virus in their gut. This project is funded by the Erichsen Family Memorial Foundation.

About the study

The researchers began by studying Danish patients who had experienced a serious bloodstream infection caused by the gut bacterium Bacteroides fragilis. They compared bacterial samples from patients who later developed colorectal cancer with samples from patients who did not develop the disease.

The finding was subsequently examined in stool samples from 877 individuals with and without colorectal cancer from several countries to determine whether the same viruses occurred more frequently in patients with cancer.

The study was supported by the Region of Southern Denmark, the Harboe Foundation and the Novo Nordisk Foundation.