Colorectal cancer is the third most common cancer in modern humans. Again and again, the bacterial species, Fusobacterium nucleatum, is recovered from colon cancer specimens resected from people diagnosed with the condition. There are other microbial species recovered, such as E. coli, Clostridium difficile, Bacteroides fragilis, and Enterococcus faecium, also, but let’s focus on this one microbe that is increasingly looking like a causal factor in cases of colon cancer.
One of the difficulties in identifying microbial species associated with colon cancers is in distinguishing microbes that are a result of the cancer or whether the microbes may have played a role in causing the cancer. F. nucleatum is increasingly looking like a causative agent: activation of cancer-causing pathways such as induction of genetic mutations in colon cells; introduction of this species into an animal’s colon causes cancer; and it has been found in pancreatic cancers. (Incontrovertible proof that F. nucleatum is a causative factor in human colon cancer would require implanting it into healthy people to see if they get cancer—no one would submit to such an unethical study, of course, so this level of proof is not possible.) In one study, for instance, F. nucleatum was present in 74% of people with colon cancer in numbers 250-fold greater than in healthy controls. In another study, high numbers of F. nucleatum were associated with lymph node metastases in 59% of cases and 0% in those with low numbers of F. nucleatum. In short, F. nucleatum is a nasty player in the microbiome world with many of the markings of a causative factor in colon cancer.
But here is the real kicker: Where does all that F. nucleatum come from? This microbial species originates in the mouth where it is the most abundant of all species. It also present at greater numbers with gingivitis and periodontitis and has been found in oral cancers. You would logically surmise that, if F. nucleatum is present at high numbers in the oral cavity, even greater if mouth infections like gingivitis or periodontitis take root, swallowing saliva abundant with the microbe would be the most likely way it reaches the colon. An elegant series of experiments by a research group in Israel demonstrated, however, that oral F. nucleatum does not reach the colon by swallowing saliva, but travels to the colon by entering the bloodstream after activities such as brushing, flossing, or chewing, achieving numbers around 10,000 microbes per milliliter of blood (!).
Add this to the growing number of observations showing that microbes residing in the gastrointestinal (GI) tract, whether mouth, stomach, small bowel, or colon, can exit the GI tract via the bloodstream and thereby take up residence in other organs. This is likely how, for instance, a probiotic such as B. infantis taken orally can colonize breastmilk and be passed onto a breastfeeding infant to enhance the child’s development, or L. reuteri taken orally can colonize the vagina and reduce Candida infections. The GI tract is not a closed system, but a system in open communication with the bloodstream and other organs.
Let’s take these arguments a step further and ask: Regardless of how a microbe like F. nucleatum reaches the colon to cause or contribute to cancer, is there something we can do to block this mouth-blood-colon connection and reduce or eliminate the development of colon cancer?
In 2021, this all remains preliminary. However, there are some commonsense and benign strategies that we can all adopt that may result in a reduced potential risk for colon cancer. You can also begin to appreciate how limited conventional “wisdom” on how to prevent cancers can be, advice to reduce consumption of red and processed meats, get more cellulose fiber, or take aspirin. How do we best manage this oral collection of roughly 100 billion microbes and 700 species that are uniquely accessible just beyond your lips? We should:
- Avoid consumption of dietary factors that cause proliferation of unhealthy species. This means avoidance of sugars and the amylopectin A of wheat and grains that trigger proliferation of species such as Streptococcus mutans that disrupts the oral microbiome.
- Just as eradication of microbes in the GI tract with an antibiotic is not a good idea and, in fact, worsens the situation, eradication of mouth microbes with mouthwash is not a solution, but a disruptive factor in the oral microbiome.
- Be mindful of oral hygiene–Including frequent brushing and flossing to prevent gingivitis, periodontitis, and reduce the burden of microbes like F. nucleatum, although such strategies are more helpful in people who continue to consume sugars and grains, less helpful in those of us who have banished such oral microbiome-disrupting factors.
- Address the intestinal microbiome—I am willing to bet that it requires more than a disrupted oral microbiome to allow a microbe like F. nucleatum to take up residence in the colon and initiate cancer. It may also require a disrupted intestinal microbiome that allow this process to occur as we know, from growing evidence, that a disrupted intestinal microbiome is a setup for cancer development.
And recall that indigenous people such as the Hadza of Tanzania, the Masaii of Kenya, the Yanomami of the Brazilian rainforest and other hunter-gatherer populations rarely have dental decay, gingivitis, or periodontitis despite engaging in virtually no efforts at oral hygiene—they have no fluoridated toothpaste, toothbrushes, dental floss, or dentists, yet maintain full mouths of teeth for their entire lifespan. They also experience virtually zero colon cancer, as well as no hemorrhoids, constipation, irritable bowel syndrome, ulcerative colitis, Crohn’s disease and other abdominal complaints. They have, of course, infections, infestations with worms, and injury, but none of the gastrointestinal “diseases of civilization” afflicting modern people. And, of course, they have very different oral and intestinal microbiomes. I believe that these situations have important lessons for us modern humans.