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Fred Hutch Researchers Identify Oral Bacteria That Appear to Play a Role in Certain Colon Cancers

Discovery highlights how ongoing microbiome research points to new opportunities that can lead to development of more effective cancer screening clinical laboratory tests

New research from the Fred Hutchinson Cancer Center in Seattle once again demonstrates that the human microbiome plays a sophisticated role in many biological processes. Microbiologists and anatomic pathologists who diagnose tissue/biopsies will find this study’s findings intriguing.

This breakthrough in colon cancer research came from the discovery that a “subspecies” of a common type of a bacteria that resides in the mouth and causes dental plaque also “shields tumor cells from cancer treatment,” according to NBC News.

The scientists inspected colorectal cancer (CRC) tumors and found that 50% of those examined featured a subspecies of Fusobacterium nucleatum (F. nucleatum or Fn) and that this anaerobic bacterium was “shielding tumor cells from cancer-fighting drugs,” NBC News noted. Many of these tumors were considered aggressive cases of cancer. 

“The discovery, experts say, could pave the way for new treatments and possibly new methods of screening,” NBC News reported.

The Fred Hutchinson Cancer Center scientists published their findings in the journal Nature titled, “A Distinct Fusobacterium Nucleatum Clade Dominates the Colorectal Cancer Niche.”

“Patients who have high levels of this bacteria in their colorectal tumors have a far worse prognosis,” Susan Bullman, PhD (above), who jointly supervised the Fred Hutch research team and who is now Associate Professor of Immunology at MD Anderson Cancer Center, told NBC News. “They don’t respond as well to chemotherapy, and they have an increased risk of recurrence,” she added. Microbiologists and clinical laboratories working with oncologists on cancer treatments will want to follow this research as it may lead to new methods for screening cancer patients. (Photo copyright: Fred Hutchinson Cancer Center.)

Developing Effective Treatments

Susan Bullman, PhD, Associate Professor of Immunology at MD Anderson Cancer Center, who along with her husband and fellow researcher Christopher D. Johnston, PhD, Assistant Professor at Fred Hutchinson Cancer Center, jointly supervised an international team of scientists that examined the genomes of 80 F. nucleatum strains from the mouths of cancer-free patients and 55 strains from tumors in patients with colorectal cancer, according to the National Institutes of Health (NIH). The NIH funded the research.

The researchers targeted a subspecies of F. nucleatum called F. nucleatum animalis (Fna) that “was more likely to be present in colorectal tumors. Further analyses revealed that there were two distinct types of Fna. Both were present in mouths, but only one type, called Fna C2, was associated with colorectal cancer” the NIH wrote in an article on its website titled, “Gum Disease-related Bacteria Tied to Colorectal Cancer.”

“Tumor-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumor niche,” the Fred Hutch researchers wrote in their Nature paper.

“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,” Johnston told the NIH.

How Bacteria Got from Mouth to Colon Not Fully Understood

Traditionally, F. nucleatum makes its home in the mouth in minute quantities. Thus, it is not fully understood how these bacteria travel from the mouth to the colon. However, the Fred Hutch researchers showed that Fna C2 could survive in acidic conditions, like those found in the gut, longer than the other types of Fna. This suggests that the bacteria may travel along a direct route through the digestive tract.

The study, which focused on participants over 50, comes at a time when colorectal cancer rates are trending upward. Rates are doubling for those under 55, jumping from 11% in 1995 to 20% in 2019. CRC is the second-leading cancer death and over 53,000 will succumb to the disease in 2024, according to NBC News.

Many of the newer diagnoses are in later stages with no clear reason why, and the Fred Hutch scientists are trying to understand how their findings tie into the increase of younger cases of colon cancer.

Bullman says it will be important to look at “whether there are elevated levels of this bacterium in young onset colorectal cancer, which is on the rise globally for unknown reasons,” she told NBC News.

Possibility of More Effective Cancer Screening

There is hope that scientists equipped with this knowledge can develop new and more effective screening and treatment options for colon cancer, as well as studying the microbiome’s impact on other diseases.

On the prevention side, researchers have seen that in mice the addition of Fna “appeared to cause precancerous polyps to form, one of the first warning signs of colorectal cancer, though Bullman added that this causation hasn’t yet been proven in humans.” NBC reported.

Future research may find that screening for Fna could determine if colorectal tumors will be aggressive, NIH reported.

“It’s possible that scientists could identify the subspecies while it’s still in the mouth and give a person antibiotics at that point, wiping it out before it could travel to the colon,” Bullman told NBC News. “Even if antibiotics can’t successfully eliminate the bacteria from the mouth, its presence there could serve as an indication that someone is at higher risk for aggressive colon cancer.”

There is also the thought of developing antibiotics to target a specific subtype of bacteria. Doing so would eliminate the need to be “wiping out both forms of the bacteria or all of the bacteria in the mouth. Further, it’s relevant to consider the possibility of harnessing the bacteria to do the cancer-fighting work,” NBC noted.

“The subtype has already proven that it can enter cancer cells quite easily, so it might be possible to genetically modify the bacteria to carry cancer-fighting drugs directly into the tumors,” Bullman told NBC News.

Further studies and research are needed. However, the Fred Hutch researchers’ findings highlight the sophistication of the human microbiome and hint at the potential role it can play in the diagnosis of cancer by clinical laboratories and pathology groups, along with better cancer treatments in the future.

—Kristin Althea O’Connor

Related Information:

A New Type of Bacteria was Found in 50% Of Colon Cancers. Many Were Aggressive Cases.

Gum Disease-related Bacteria Tied to Colorectal Cancer

A Distinct Fusobacterium Nucleatum Clade Dominates the Colorectal Cancer Niche

Effort to Map Human Microbiome Will Generate Useful New Clinical Lab Tests for Pathologists

Human Microbiome Project is expected to trigger many new molecular diagnostic assays

Meet the human microbiome, considered by some medical researchers to be the newest biomedical frontier. A major effort to map the human microbiome is expected to identify a significant number of new biomarkers that will be useful in both clinical pathology diagnostic tests and therapeutic drug development.

Known as the Human Microbiome Project, the five-year program is funded with $115 million in grants from the National Institutes of Health (NIH). Researchers are well on their way to produce a comprehensive inventory of microbes—bacteria, viruses, yeast and fungi—that live in or on the human body, along with information about their role in disease development or prevention. The overall goal of this international effort is to identify which microbes are harmful and figure out ways to prevent or treat diseases they cause.