Can Oral Microbes Cause Dementia?

Microbes in the mouth have an outsize influence on brain health.

Posted Dec 21, 2020

The gut microbiota is enjoying a renaissance. Everywhere you look, some kind of health issue is being traced back to gut microbes. Fortunately, gut microbiotas have been found to be largely beneficial unless — like a jungle with too many tigers — they get ecologically unbalanced.

Scott Anderson and Anetlanda/iStock
Oral microbes can affect your brain.
Source: Scott Anderson and Anetlanda/iStock

The impact of the gut on health isn’t new. Hippocrates proclaimed that all disease starts in the gut some 2500 years ago before anyone knew about bacteria. Now we know that microbes liberally carpet the entire length of the digestive system. The biggest batch is in the colon, where some three pounds of bacteria enjoy a thriving community. But they exist throughout the entire gut, from mouth to anus. And there is a surprising impact on the brain from microbes living in the mouth, which are, after all, sharing space in your head.

What are all these microbes doing there?

A lot, it turns out. Everything you need to make life is coded by genes that specify how to build proteins. Humans have 20,000 genes, which is surprisingly sufficient to create a person. But we have about a thousand species of bacteria living in and on our body — each with about two thousand genes — so the combined number of microbial genes is two million. In other words, by far most of the genes available to us are microbial. In this genetic sense, we are only 1 percent human!

These genes allow microbes to make sugars, fatty acids, toxins, and, surprisingly, neurotransmitters — the same chemicals used by nerve cells in our brain to help us form thoughts and memories. Since microbes don’t have brains, these neurotransmitters are likely used by them to communicate with each other. However, there is mounting evidence that these microbes may also be communicating directly with us. Microbes may produce dopamine and serotonin in response to favored foods, potentially steering our cravings. Microbes can thus alter our thinking and have been shown to alter our moods. Those that reduce anxiety and depression are called psychobiotics.

If the gut gets leaky and allows microbes to enter the bloodstream, even beneficial microbes can be bad. The blood-brain barrier protects the pristine brain from the rough and tumble of the body, and it does a good job of keeping out microbes. But over time, toxins from those microbes may leak into the brain.

There’s accumulating evidence that brain diseases like dementia, Alzheimer’s and Parkinson’s may start in the gut. Earlier this month, a large, 16-year Taiwanese study reported that people with inflammatory bowel disease were more likely to have dementia and to be diagnosed earlier. The connection between the gut and the brain — a wild idea just a decade ago — is now well established.

What about oral microbes?

Most of this research has concentrated on these gut microbes, leaving the relatively small populations in the mouth understudied. What we do know is that oral microbes are associated with several systemic diseases, including heart disease, lung cancer, arthritis, stroke, and cancer. To that bleak list, we can add brain diseases like dementia and Alzheimer’s.

One of the most successful pathogens of the oral microbiota is Porphyromonas gingivalis, the bad actor behind gingivitis. Instead of hanging out between the cells of your body where it can be plucked off by patrolling immune cells, P. gingivalis burrows directly into cells where it can hide out. It uses several tricks to subvert attack by the immune system and once entrenched, it’s devilishly hard to remove.

It is a keystone species in the making of biofilms, the king of the microbial jungle. Merely brushing or flossing your teeth can break down tissues enough to let P. gingivalis escape the mouth and enter the bloodstream, where it can reach any organ or tissue in the body. Chronic periodontitis is a significant risk factor for developing Alzheimer’s and dementia. P. gingivalis is omnipresent in the arteries of heart disease patients and has recently been found in the brains of 96 percent of Alzheimer’s patients, significantly more than normal controls. It typically co-occurs with the amyloid plaques that are hallmarks of the disease.

Drugs that block gingipain, the toxin produced by P. gingivalis, can halt brain inflammation and rescue neurons, demonstrating a causal role for this microbe. These drugs, if they make it through clinical trials, may represent a future therapy.

It probably shouldn’t surprise us that both the mouth and the gut are implicated in brain disease. They are just opposite ends of the same pipe. With a liter of bacteria-laden saliva being swallowed every day, it isn’t hard to imagine that a lot of microbial ecology gets shared, all the way down.

What can be done?

You shouldn’t stop brushing or flossing, although you can attempt to not draw blood while doing it. Oral probiotics are available, but there is limited data on their effectiveness against pathogens like P. gingivalis.

Diet plays a major role. As with gut bacteria, fiber is key. Fiber is composed of long sugar chains that are resistant to digestion but are favored food for microbes. Fiber is only found in vegetables and fruits, not meat. So eat your veggies.

Many otherwise healthy people, including athletes, eat a lot of junk food in the form of energy drinks and power bars that are loaded with sugar. We know that sugar is bad for our teeth, but it’s also bad for the balance of microbes in your mouth. So try to minimize sugar in your diet.

Also, drink more water. You need to stay hydrated to ensure plenty of saliva, which contains proteins and mucins specifically to feed the beneficial bacteria in your mouth.

Bottom line: Take care of your mouth. It has a shocking amount of control over your mental health — now and into your future.

References

Maitre, Yoann, Pierre Micheneau, Alexis Delpierre, Rachid Mahalli, Marie Guerin, Gilles Amador, and Frederic Denis. “Did the Brain and Oral Microbiota Talk to Each Other? A Review of the Literature.” Journal of Clinical Medicine 9, no. 12 (November 28, 2020): 3876.

Marizzoni, Moira, Annamaria Cattaneo, Peppino Mirabelli, Cristina Festari, Nicola Lopizzo, Valentina Nicolosi, Elisa Mombelli, et al. “Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer’s Disease.” Journal of Alzheimer’s Disease 78, no. 2 (January 1, 2020): 683–97.

Zhang, Bing, Hohui E. Wang, Ya-Mei Bai, Shih-Jen Tsai, Tung-Ping Su, Tzeng-Ji Chen, Yen-Po Wang, and Mu-Hong Chen. “Inflammatory Bowel Disease Is Associated with Higher Dementia Risk: A Nationwide Longitudinal Study.” Gut 70, no. 1 (January 1, 2021): 85–91.

Mougeot, Jean-Luc, C. Stevens, Bruce Paster, M. Brennan, P. Lockhart, and F. Mougeot. “Porphyromonas Gingivalis Is the Most Abundant Species Detected in Coronary and Femoral Arteries.” Journal of Oral Microbiology 9 (February 8, 2017): 1281562.

Dominy, Stephen S., Casey Lynch, Florian Ermini, Malgorzata Benedyk, Agata Marczyk, Andrei Konradi, Mai Nguyen, et al. “Porphyromonas Gingivalis in Alzheimer’s Disease Brains: Evidence for Disease Causation and Treatment with Small-Molecule Inhibitors.” Science Advances 5, no. 1 (January 1, 2019): eaau3333.