Mouth Bacterium Subtype Found in Half of Colon Cancer Tumors

Mouth Bacterium Subtype Found in Half of Colon Cancer Tumors
24.03.2024
  • A certain subtype of a bacterium commonly found in the mouth showed up in 50% of colorectal cancer tumors examined by researchers.
  • This bacterium subtype was also found in 30% of stool samples from people with colorectal cancer.
  • Previous research showed that this bacterium, when present in the tumor, is linked to worse outcomes in patients with colorectal cancer.

A specific subtype of a bacterium commonly found in the mouth can grow within colorectal cancer tumors, and can travel there through the gut, researchers found.

Earlier research has shown that patients whose colorectal tumors have high amounts of this type of bacterium, known as Fusobacterium nucleatum, have poorer clinical outcomes.

The results of the new study, published Mar. 20 in Nature, could help scientists develop new treatments or ways to screen for colorectal cancer earlier.

Colorectal cancer is the second most common cause of cancer deaths in adults in the United States, expected to result in over 53,000 deaths in 2024, according to the American Cancer Society. Also known as colon cancer or rectal cancer, this affects the lower part of the gut, or intestinal tract.

Bacterium linked with colorectal cancer

In the new study, researchers examined colorectal tumors from over 200 patients, looking for the presence of Fusobacterium nucleatum.

“This bacterium is thought to be part of the normal mouth microbiome,” said study author Susan Bullman, PhD, an assistant professor at the Fred Hutchinson Cancer Center in Seattle. But “usually you don’t see it in the lower intestines.”

The microbiome is the collection of bacteria, viruses and other microbes that reside in and on our body, and contribute to health and disease.

About a decade ago, Fusobacterium nucleatum gained attention when scientists found that it was linked with colorectal cancer.

When colorectal cancer develops, Fusobacterium nucleatum dominates the microbiome in the tumors of certain patients, Bullman told Healthline, something she and her colleagues saw in their study.

In about half of the tissue samples they examined, a specific subtype of this bacterium was present in higher amounts compared to healthy tissue.

This subtype was also found in higher amounts in stool samples from some patients with colorectal cancer compared to stool samples from healthy people.

Identifying which subtypes are involved

One goal of the new study was to understand which types of Fusobacterium are linked to colorectal cancer.

“Is there a specific high-risk group of Fusobacterium that are actually getting to the colorectal tumor and leading to cancer progression?” asked Bullman.

The findings confirm that it is mainly a certain subtype of this bacterium which moves from the mouth to the colorectal tumor.

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In addition, the researchers discovered that the main group of Fusobacterium nucleatum involved in colorectal cancer is not a single subspecies, but is actually two distinct subtypes known as “clades.”

While both clades colonize the mouth, only one of these, known as Fna C2, was found in significantly higher amounts in colorectal tumors, showing up in about 50% of tissue samples.

“[Fna C2] is a high-risk subtype that’s actually getting to the lower gastrointestinal tract and promoting tumor growth,” said Bullman.

This subtype was also found in about 30% of stool samples from patients with colorectal cancer, as well as about 5% of stool samples from healthy people.

Other bacteria may play a role

Weinberg said the fact that Fna C2 didn’t show up in tissue and stool samples from all patients with colorectal cancer suggests that the bacterium may not play a role in the progression of their cancer.

However, that doesn’t mean other bacteria aren’t involved.

Weinberg’s research focuses on the microbiome inside colorectal tumors, with an interest in understanding why there has been a rise over the past few decades in colorectal cancer among people under age 50.

In a study published last year in the Journal of Clinical Oncology, he and his colleagues identified differences in the types of bacteria found in tumors of people diagnosed with colorectal cancer before age 45 compared to after age 65.

So, is Fna C2 leading to the development of colorectal cancer or just moving into the tumor once it starts growing?

The authors of the new study did try to answer this question using experiments done in mice.

These results, though, “[reveal] limited, if any, cancer-promoting potential of Fusobacterium species in susceptible mouse models,” wrote the authors of a related editorial in Nature, although they suggest it may be due to the limitations of this kind of experiment.

Overall, “it’s hard to say how much [Fna C2] itself is involved in the carcinogenic process,” said Weinberg.

He suggests that Fna C2 might act “more like a chaperone, where these tumors arise and this bacterium helps them grow and spread.”

Supporting this, a 2017 study in Science by Bullman and her colleagues found that Fusobacterium nucleatum was present in colorectal tumors that had spread to other parts of the body.

“So clearly, [this bacterium] is at least along for the ride,” said Weinberg.

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Bacterium travels via gut

Some earlier research suggested that Fusobacterium nucleatum might get into the bloodstream when people cleaned their teeth or had a dental procedure, after which it would make its way to the colorectal tumor.

Other bacteria are suspected of traveling this route to other tissues in the body to cause a variety of health conditions, including heart disease.

However, Bullman and her colleagues found evidence that Fna C2 could travel through the gut, which requires it to survive the highly acidic environment of the stomach.

A genetic analysis revealed 195 genetic differences between the two Fusobacterium nucleatum clades. This analysis also showed that Fna C2 had distinct genetic traits that would allow it to withstand stomach acid and grow in the lower intestinal tract.

“[The authors] show that Fna C2 has some features which might enable it to survive in a more acidic environment,” said Weinberg, “whereas the [other subtype] may not.”

Earlier cancer screening possibilities

More research is needed to fully understand the role of this subtype of Fusobacterium nucleatum in colorectal cancer.

“From our analysis, we are seeing [Fna C2] in the mouth of what we consider to be presumably healthy individuals,” said Bullman. “But whether or not those individuals…are at higher risk for colorectal cancer, we don’t have that information yet.”

To determine that, larger and long-term studies would be needed. This might involve analyzing people’s mouth microbiome for the presence of Fna C2, and then following them for a decade or longer to see how many people develop colorectal cancer.

Bullman said the development of colorectal cancer will likely depend on more than just the presence of this bacterial subtype.

So any long-term study would also need to take into account other factors known to increase the risk of colorectal cancer, such as diet and use of tobacco or alcohol.

More immediately, looking for the presence of Fna C2 in a stool sample might provide a non-invasive way of screening for colorectal cancer.

“This particular subtype was elevated in the stool of patients with colorectal cancer compared to those without colorectal cancer,” said Bullman. “So from a screening perspective, that could be valuable.”

More research would be needed to show whether Fna C2 is also present in stool samples from people with earlier stages of colorectal cancer, such as precancerous lesions or adenomas.

Another screening option would be to use a blood test to look for Fna C2 or other bacteria linked to colorectal cancer.

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“[My colleagues and I] have some research trying to look at the circulating microbiome,” said Weinberg. “Basically, can we detect bacterial DNA in the bloodstream?”

If a blood test shows that certain people have a microbiome that gives them a higher risk of developing colorectal cancer, that group of people could be screened earlier with a colonoscopy, he said.

Targeting cancer with new treatments

Knowing which specific subtype of Fusobacterium nucleatum is involved in colorectal cancer might also enable scientists to develop new treatments.

In an earlier study published in 2017 in Science, Bullman and her colleagues implanted colon tumors obtained from human patients into mice. Mice that were treated with an antibiotic that targeted Fusobacterium nucleatum showed reduced tumor growth.

“So there is evidence that targeting this microbe can reduce tumor growth,” said Bullman. “And that was just an antibiotic.”

The goal, though, would be to eliminate just this specific subtype.

“We don’t want to eliminate all Fusobacterium nucleatum if they’re not actively contributing to disease,” said Bullman. “The key here is to maintain the microbiome in a somewhat normal structure.”

This might be done using targeted inhibitors, which could be coupled with standard chemotherapy or immunotherapy, “to see if that can enhance efficacy of routine treatment approaches,” said Bullman.

Another possible treatment approach would be to put the bacterium’s own abilities to good use.

“Because [this subtype] travels to the tumor, we’re thinking about how we can engineer it to deliver drugs that kill the tumor,” said Bullman.

This “bug as a drug” approach, as it’s called, would use an attenuated version of the bacterium, one that can’t cause disease but can still get into the colorectal tumor.

Takeaway Note

Researchers identified a specific subtype of the bacterium Fusobacterium nucleatum that is involved in colorectal cancer. This subtype was found in 50% of tumor samples and 30% of stool samples collected from people with colorectal cancer.

A genetic analysis showed that this subtype had specific traits which would allow it to pass from the mouth to the lower gut and grow there. This includes being able to withstand the acidic environment of the stomach.

These findings could lead to new ways to screen earlier for colorectal cancer or treatments for this cancer, which is the second most common cause of cancer deaths in adults in the United States.

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