Colorectal cancer—cancer of the colon and rectum—is the fourth most common cancer nationwide. Although overall rates have been steadily falling due to better screening techniques, rates of colorectal cancer in young adults are on the rise. Researchers have been working hard to understand the causes.
A bacteria implicated in gum disease, Fusobacterium nucleatum, has also been found in some colorectal cancer tumors. F. nucleatum is rarely seen in the guts of healthy people. Colorectal tumors harboring these bacteria are associated with more cancer recurrence and worse patient outcomes than tumors without them. However, it’s unclear how much of a role, if any, the bacteria play in causing the tumors to grow.
F. nucleatum is normally found in low levels in the mouth but can flourish and, along with other microbes, trigger inflammation to cause gum, or periodontal, disease. Over time, this inflammation can lead to destruction of the bone and tissues that support the teeth, resulting in tooth loss. Studies over the years have pointed to a relationship between periodontal disease and other conditions throughout the body, including those of the heart, kidneys, autoimmune diseases, and even some cancers. However, in most cases scientists still don’t entirely understand the degree of involvement, if any, that periodontal disease has in causing these conditions.
An NIH-funded research team led by Drs. Martha Zepeda Rivera, Susan Bullman, and Christopher D. Johnston of the Fred Hutchinson Cancer Center did a careful genetic comparison between F. nucleatum from colorectal tumors and those from healthy mouths. They analyzed the genomes of 80 F. nucleatum strains from the mouths of people without cancer and 55 strains from tumors of patients with colorectal cancer. The findings were published on March 20, 2024, in Nature.
The team found that one subspecies of F. nucleatum, called Fna, 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.
When the researchers infected mice that had inflamed intestines (an animal model of colitis) with these two types of F. nucleatum, they found that mice infected with Fna C2 developed more tumors than those infected with the other type.
It’s not quite known yet how these bacteria travel from the mouth to the colon. However, the researchers showed that Fna C2 could survive longer in acidic conditions, like those found in the gut, than the other type of Fna. This suggests that the bacteria may travel along a direct route through the digestive tract.
“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer,” Johnston says, “and that knowledge is critical for developing effective preventive and treatment methods.”
Future studies can test if specifically targeting F. nucleatum in colorectal tumors can improve patient outcomes. Clinicians might also one day be able to screen for Fna C2 to identify colorectal tumors that are more likely to be aggressive.
—by Vanessa McMains, Ph.D.
The Health of Your Mouth May Affect Your Risk of Colorectal Cancer
Could the health of your mouth, gums, and teeth influence the likelihood of developing cancer or make tumors grow more aggressively? A growing body of evidence suggests that the presence of gum disease is linked with an increased risk of several types of cancer, especially colorectal and pancreatic cancer. Gum disease is a set of inflammatory conditions affecting the tissues surrounding the teeth.
Colorectal cancer (cancer of the colon and rectum) is the third-leading cause of cancer-related death for men and the fourth-leading cause for women in the United States.
Although overall rates have been steadily falling due to better screening techniques, rates of colorectal cancer in young adults are rising. It’s likely that those increases are a combination of many factors, including sitting too much, being overweight or having obesity, and a diet high in processed foods and low in fiber.
The Mouth Is the Second Largest Microbiome in the Body
Another potential factor behind the uptick is a bacteria that’s found in the mouth microbiome of people with gum disease. Although much has been written about the largest microbiome in the body, the gut microbiome, the mouth contains the second largest and diverse microbiome, with over 700 species of bacteria.
The mouth’s microbiome and the balance of bacteria within it influences overall health in many ways, says Mingyang Song, ScD, an associate professor of clinical epidemiology and nutrition at the Harvard T.H. Chang School of Public Health in Boston. Dr. Song has published research on the connection between the oral microbiome and colorectal cancer.
Researchers have zeroed in on a few bacteria that may be especially important in terms of health, including Fusobacterium nucleatum, which is normally found in low levels in the mouth, but can flourish and contribute to inflammation and gum disease. Left untreated, gum disease can eventually lead to destruction of the bone and tissues that support the teeth, causing tooth loss.
Gum Disease and Tooth Loss Linked to Increased Colorectal Cancer Risk
The health of the mouth microbiome has also been linked to a variety of diseases outside of the mouth, including cancer, obesity, diabetes, heart disease, Alzheimer disease, inflammatory bowel disease, rheumatoid arthritis, and metabolic dysfunction–associated steatotic liver disease, says Song. There’s also a relationship to a few types of cancer, including cancers of the head and neck. It’s most consistently associated with colorectal and pancreatic cancers, he adds.
But scientists still don’t entirely understand the degree of involvement, if any, that gum disease and the mouth microbiome has in causing these conditions.
Song was a senior researcher in two studies that found a link between cancer and gum disease. In the first, researchers found that people with a history of gum disease had a 52 percent greater risk of stomach cancer compared with people without gum disease, and having lost two or more teeth increased stomach cancer risk by 33 percent. Gum disease was also linked to an increased risk of esophageal cancer.
In the second study, Song and colleagues found that gum disease is also linked with an increased risk of colorectal cancer. Compared with people with no history of gum disease, those who had gum disease had a 17 percent increased relative risk of having a serrated polyp.
A serrated polyp is a type of colon polyp that can eventually turn into cancer — about 25 percent of colon cancer cases develop from this type of polyp.
Researchers also found that the loss of four or more teeth was linked with a 20 percent increased risk for having a serrated polyp.
A history of gum disease was associated with an 11 percent increased risk of a conventional adenoma, another type of colon polyp that is noncancerous, but can eventually turn into cancer.
In both those studies, the authors pointed to a possible disruption in the mouth microbiome that could be related to poor oral hygiene, genetics, smoking, diabetes and obesity. Compared with healthy individuals, the people diagnosed with colorectal cancer had higher transmission rates of the harmful F. nucleatum from the mouth to the gut.
Imbalances in the Mouth Microbiome Can Cause Inflammation
How does harmful bacteria in the mouth potentially affect other parts of the body, including colorectal cancer? That isn’t totally clear; both direct and indirect ways have been proposed, says Song.
The oral microbes can directly get to the other parts of the body and cause damage and inflammation, he says. “Also, alterations in the oral microbiome can cause systemic inflammation and increase disease risk indirectly.”
How Mouth Bacteria Travels to Other Parts of the Body
And how does the bacteria get to the G.I. tract or the bloodstream? There are a couple of ways that can happen, says Floyd Dewhirst, DDS, PhD, an emeritus professor of oral medicine, infection, and immunity at Harvard Medical School in Boston. Dr. Dewhirst has been studying the mouth microbiome for decades.
“Basically, the fate of almost all the bacteria that live in the mouth is at some point to get swept up by saliva and swallowed,” he says. Following the path down, the bacteria go through the stomach, and if they survive the acid treatment of the stomach, they could make it to the GI tract, says Dewhirst.
There are also lots of bacteria that can cause infection in your periodontal and subgingival pockets (the spaces or openings surrounding the teeth under the gum line and where the tooth connects to the gum) in people who have gum disease, he says.
“When you do things like bite into an apple or brush your teeth, a small number of these organisms are able to get into the bloodstream from the vessels that are next to the gum tissue. Most of the time the body is good at finding the small number of bacteria and destroying it, but occasionally, something that’s gotten into the bloodstream can circulate through the body and go somewhere else and start an infection,” says Dewhirst.
You can also spread bugs from your mouth if you get saliva on your fingers and then touch your eye, nose, or scratch broken skin, he says.
Researchers Find a More Dangerous Subspecies of F. Nucleatum
Dewhirst was the coauthor of a study published in Nature in March 2024 that may help lead to better ways of identifying and targeting aggressive colon cancers.
First, researchers did a careful genetic comparison between F. nucleatum from colorectal tumors and those from healthy mouths and learned that one subspecies of the bacteria, called Fna, was more likely to be in colorectal tumors. Further study revealed that there were two distinct types of Fna. Although both types were found in mouths, only one type, Fna C2, was associated with colorectal cancer.
Investigators then infected mice that had inflamed colons with these two types of F. nucleatum. Mice infected with Fna C2 developed more tumors compared with mice infected with the other type.
Although researchers don’t know yet how these bacteria travel from the mouth to the colon, researchers showed that Fna C2 could survive longer in acidic conditions, like those found in the gut, than the other type of Fna. That could mean the bacteria travels along a direct route through the digestive tract, according to the authors.
Knowing the exact bacterial lineage that is associated with colorectal cancer is critical for prevention and targeted treatment to improve outcomes, the authors wrote.
Bottom Line: Practicing Good Oral Hygiene May Reduce Your Risk of Colorectal Cancer
While it isn’t clear how oral hygiene specifically may influence cancer risk, we know that poor oral hygiene increases risk of gum disease, says Song. “Practicing oral hygiene is certainly a good practice,” he says.
Besides that, a healthy diet and lifestyle, including regular exercise and not smoking, has also been shown to keep the oral microbiome healthy, says Song.
