Aggressive Colorectal Cancer Tied to Oral Bacterium

Discoveries involving microbes in colon cancer could eventually drive screening methods and lead to microbial-based therapies targeting tumors. 

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A new study shows that a common oral bacterium linked to a virulent form of colorectal cancer could be driving tumor growth.

The discovery was made in a study published March 20 in Nature. Researchers from Fred Hutchinson Cancer Center performed a variety of tests on human stool samples and mice to document the transfer of this bacterium, Fusobacterium nucleatum, which occurred in about half of the colorectal cancers in tumors removed from 200 patients.

Colorectal cancer causes the second-highest number of cancer deaths in U.S. adults, according to the American Cancer Society. In 2024, it’s expected to take the lives of more than 53,000 people.

Significance of Findings

Fusobacterium nucleatum is of particular interest because the patients in which it’s detected have a poorer prognosis and survival rate, Susan Bullman, Fred Hutch cancer microbiome researcher and co-corresponding study author, explained in a news release.

“Now we’re finding that a specific subtype of this microbe is responsible for tumor growth,” she said. “It suggests therapeutics and screening that target this subgroup within the microbiota would help people who are at a higher risk for more aggressive colorectal cancer.”

The specific subtype of the Fusobacterium—described as Fna C2—was found in half the tumors in the study. It was also found in higher quantities of stool samples of 627 colorectal patients compared to 619 healthy people in a separate analysis included in the study.

Fna C2 was one of two distinct lineages of Fusobacterium nucleatum noted in the colorectal tumors with 195 genetic differences from the other clade, or group of organisms with similar genetic traits, called Fna C1. Traits of Fna C2 indicate it could pass through stomach acid and then grow in the colon.

Stomach acid often inhibits the proliferation of microbes that don’t belong in the lower intestine. But a number of factors can also interfere with this protective mechanism, including bacteria that adapt to stomach acid, such as Heliobacter pylori (H. Pylori),  and having low levels of stomach acid, which increases the risk of infection.

Hope for Prevention, Screening, and Treatment

“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer, and that knowledge is critical for developing effective preventive and treatment methods,” co-corresponding author Christopher D. Johnston, Fred Hutch molecular microbiologist, said in the news release.

Still, it could be some time before those tools are developed, mostly because more research is needed, Dr. Marty Makary, a cancer surgeon at Johns Hopkins told The Epoch Times.

“One may think that preventing colon cancer could be as simple as eradicating that particular Fusobacterium bacterium from the gut. But the gut lives in an equilibrium, and when you are playing with mother nature, you may invite a problem you do not anticipate,” he said.

Gut Disruption

The gut microbiota is a collection of trillions of bacteria, viruses, fungi, and other microorganisms. Until the last several decades, attention has honed in on pathogenic microbes and antibiotics that often wipe out the whole community. Newer studies are finding a relationship between the composition of the overall microbiome and many diseases.

“We don’t know what we’re doing to the microbiome,” said Dr. Makary, a bestselling author whose latest book is “Blind Spots: When Medicine Gets It Wrong, and What It Means for Our Health.” “It may be antibiotics and other things we do may enable more inflammatory bacteria, and inflammation has been suggested to be a contributing factor to cancer.

“Something is going on. Unfortunately, the medical establishment has not valued this type of research and has massively underfunded the role of the microbiome in cancer and chronic disease.”

The Role of Antibiotics

In fact, it could be modern medicine’s interventions that have caused the disruption in the first place. Dr. Makary noted research showing a relationship between antibiotic use—which can wipe out protective microbes in the gut microbiome—and colon polyps, a potential precursor to colon cancer.

In a study of women in their 40s and 50s who used antibiotics published in 2017 in Gut, colon polyps showed up in their colonoscopies in frequency mirroring the length of their antibiotic use. Those who took antibiotics for more than two months had a 1.69 times increased risk of polyps.

Assessing antibiotic use for a two-year period, another study found those who had six or more prescriptions for antibiotics among those aged 30 to 79 had a 15 percent increased risk for colon cancer. Published in 2008 in the International Journal of Cancer, the study concluded antibiotic use can predict “an increased risk of cancer.”

“A possible theory about why antibiotics may lead to the formation of colon polyps, and later cancer, could be because they indiscriminately kill healthy gut bacteria. As this occurs, other, more unhealthy bacteria predominate in the colon, which can affect the immune response in the colon, leading to disruptions in its lining and the formation of polyps,” according to an article written by Dr. Robert Ashley, an internist and assistant professor of medicine at the University of California, Los Angeles.

Lessons From History

While the new study makes it clear there’s an association between the microbiome and colorectal cancer, Dr. Makary said it’s possible there could be many microbes involved. Moving forward, he said it’s important that medical dogma be acknowledged and for open minds to prevail in studying the microbiome as a whole.

“We’re seeing the tip of the iceberg when it comes to our understanding of the microbiome,” he said. “As long as we are only researching chemotherapy and not the exposures that cause cancer we’re never going to better understand the role of the microbiome in cancer and chronic disease.”

The possible microbial link with colon cancer raised in this study is not unlike the discovery that H. pylori can cause stomach ulcers, Dr. Makary noted.

Heliobacter pylori, a common bacteria that most people have, can sometimes damage stomach and small intestine tissues, causing a hyperinflammatory state that can lead to peptic ulcers in the upper digestive tract.

“The medical establishment laughed at the idea put forth by researchers and said, ‘We’re certain it’s stress, not one bacteria in the microbiome.’ but there was a direct relationship that was proven,” Dr. Makary said.  “If we can acknowledge we have these blindspots that deserve research with the same methodological rigor that we apply to pharma research then we can start to have meaningful discoveries to get at the rising rates of cancer in young people.”