Scientists have identified a previously unknown virus living inside a common gut bacterium that appears significantly more often in people with colorectal cancer, potentially explaining a long-standing medical puzzle about why the same microbe shows up in both sick and healthy individuals.
Colorectal cancer ranks among the most prevalent cancers in Western nations and remains a leading cause of cancer death. Researchers have long known that age, diet, and lifestyle influence risk, but the precise mechanisms driving the disease have remained murky. Recent investigation of the gut microbiome, the complex ecosystem of bacteria, viruses, and other organisms inhabiting the digestive tract, is starting to change that picture.
A team at the University of Southern Denmark and Odense University Hospital zeroed in on Bacteroides fragilis, a bacterium repeatedly linked to colorectal cancer. Yet here lay the paradox: the same bacterium thrives in most healthy people's guts, making the connection difficult to explain.
"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, a medical doctor and researcher at Odense University Hospital and the University of Southern Denmark.
The breakthrough came when researchers investigated whether something inside the bacterium itself might differ between cancer patients and the general population. They discovered the answer: a bacteriophage, a virus that infects bacteria and had not been previously identified.
In patients who went on to develop colorectal cancer, Bacteroides fragilis was far more likely to carry this specific virus. The virus appears to represent entirely new types never before documented.
"It is not just the bacterium itself that seems interesting. It is the bacterium in interaction with the virus it carries," Damgaard explains.
The research began with data from a massive Danish population study tracking roughly two million people. Researchers examined patients who had suffered serious bloodstream infections from Bacteroides fragilis. A small subset of these individuals developed colorectal cancer within weeks. By comparing bacterial samples from cancer patients against those without the disease, a clear pattern emerged: bacteria from cancer patients harbored these specific viruses at much higher rates.
To verify the finding extended beyond Denmark, the team analyzed stool samples from 877 individuals across Europe, the United States, and Asia. The pattern held. People with colorectal cancer were approximately 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," Damgaard says.
The consistency strengthens the connection but stops short of proving the virus directly causes cancer. "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," he notes.
Researchers estimate that up to 80 percent of colorectal cancer risk stems from environmental factors, including the microorganisms inhabiting the digestive system. The gut microbiome contains thousands of bacterial species and vastly more genetic variation, making it historically difficult to isolate 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," Damgaard says.
If the virus alters how the bacterium functions, it could reshape the gut environment in ways that influence cancer risk. That possibility is now under investigation through multiple ongoing projects. One involves growing the virus-carrying bacterium in an artificial gut model to study how the virus, bacterium, and gut tissue interact. Another will inject the bacterium and virus directly into colorectal cancer tumors to examine their presence within tumor tissue. A third will test whether mice genetically predisposed to cancer develop the disease faster if they carry the virus-infected bacterium.
The findings suggest potential new screening approaches. Current colorectal cancer screening typically uses stool tests to detect hidden blood. In the future, testing for these newly identified viruses could identify individuals at elevated risk. Early analysis indicates that certain viral markers could identify about 40 percent of cancer cases, while most healthy people do not carry them.
Researchers caution the work remains preliminary. More studies are required before any viral screening tool could move into clinical use. "In the short term, we can investigate whether the virus can be used to identify individuals at increased risk," Damgaard says.
Author Jessica Williams: "This discovery transforms how we think about cancer risk in the microbiome, but the team is right to pump the brakes until they prove the virus actually pulls the trigger."
Comments