Why tending your oral microbiome is the secret to a long, healthy life

There are untold legions of viruses, fungi and bacteria living in your mouth. It now seems we can stave off conditions from Alzheimer’s disease to cancer by keeping them in a healthy balance.

It is always the same vibe: the glossy, out-of-date magazines, the smell of sterilising fluid, the inevitable fish tank. Dentists’ waiting rooms aren’t much fun, and when you go through to the surgery, it only gets worse. The chair tilts back with an electric whir, the masked face says “open wide” and out comes an array of sharp, metal implements. No wonder many of us emerge rubbing our gums and wondering how long we can put off our next appointment. 

But perhaps we need to recalibrate our relationship with our oral health, because there is a consensus emerging that looking after it might be the underappreciated secret to a longer, healthier life. 

What matters isn’t so much having pearly whites per se, but looking after our oral microbiome: the viruses, fungi and 700 or so species of bacterium that reside in our mouths. Let our oral hygiene slip, and bad bacteria from there can travel all over the body, causing or exacerbating problems, from cardiovascular disease and cancer to Alzheimer’s disease and arthritis. Keeping everything in balance, on the other hand, staves off decline.

Here’s the good news: now we are coming to understand the importance of the oral microbiome, there are things we can do to keep it in tip-top condition. That doesn’t just mean brushing and flossing, but could include new vaccines against gum disease and even bathing your gums in an oral microbiome re-placement composed of microbes from our long-lost hominin ancestors. Going to the dentist won’t be any more pleas-ant, but we have all the more reason to grin and bear it. 

Over the past decade or so, biologists have shown that we are festooned with microbes, inside and out. This microbiome, composed of bacteria, fungi and viruses, profoundly influences who you are. It is the gut microbiome that gets the most limelight. We know it influences our health and fitness and is even linked to our emotional state. 

The oral microbiome gets far less attention, but we have known of it for a long time. In 1891, US dentist Willoughby D. Miller first proposed that bacteria could leave the mouth, travel toot her parts of the body and cause dis-ease. Frank Billings, co-founder of the Institute of Medicine of Chicago, later speculated that tooth infections may be the cause of rheumatoid arthritis, among other diseases.

We only began to get supporting evidence in 1989, when Kimmo Mattila, a doctor at Helsinki University Central Hospital in Finland, and colleagues noticed that people who had experienced a heart attack were rated as having oral health that was about twice as poor as that of a control group, even when age, social class and smoking habits were accounted for. A solid link seemed to be there.

More recently, DNA sequencing technology has improved apace, enabling us to catalogue the microbes in our mouths. Thanks to this, we are now finding that the types of bacteria people have living there seem to be associated with a growing number of conditions. We know, for instance, that people with gum disease are as much as 20 percent more likely to get cancer in their life-times compared with otherwise healthy people. 

Alzheimer’s and gum disease 

But perhaps the most striking example is Alzheimer’s disease. We have known for a while that people with gum disease are at increased risk of developing this condition, which slowly robs people of their memories, personalities and cognitive function. However, until recently, it was unclear whether poor oral health was a contributing cause of Alzheimer’s or a consequence of it.

Then, in 2019, scientists discovered species of bacteria known to cause gum disease – including one called Porphyromonas gingivalis – living inside the brains of people who died of Alzheimer’s disease. There were also gingipains, protein-degrading enzymes produced by P. gingivalis, in their hippocampi, a region of the brain responsible for memory. Meanwhile, mice with chronic gum disease were found to have inflammation, neural damage and build-ups of beta-amyloid protein plaques in their brains – one of the hallmarks of Alzheimer’s disease. If the mouth bacteria were getting into the brain that lent weight to the idea that they could be a cause of Alzheimer’s. 

We are also starting to grasp how this could happen. The biology of the mouth makes it a vulnerable point. Where the teeth meet the gums is a tiny gap called a sulcus. In a person with healthy teeth and gums, this gap is small, but if you don’t brush properly, bacteria can build up, causing inflammation. As the gums become more inflamed, they start to pull away from the teeth, and a deeper pocket forms. Harmful bacteria can hide and multiply in this airless environment, and then, if you have bleeding gums, they can get into your bloodstream. “The teeth are the weakest link of the body,” says periodontologist Alpdogan Kantarci at the Forsyth Institute in Cambridge, Massachusetts. 

But thanks to our immune systems, the survival time of foreign microbes in a person’s bloodstream is usually minimal. So, how can bacteria reach the brain? Intriguingly, in a study earlier this year, Kantarci and his collaborators showed that oral bacteria could be hitching a lift inside the body’s own immune cells. His team took neutrophils, a type of white blood cell, from people with no significant health issues. These cells are experts at gobbling up invading bacteria. However, when Kantarci and his colleagues introduced them to Fusobacterium nucleatum, a bacterium commonly found in the mouth, the microbes survived being swallowed by the neutrophils. Rather than killing them, the white blood cells acted like Trojan horses, protecting the bacteria from other immune cells and transporting them over large distances. After travel-ling for a while, the neutrophils broke apart, releasing their dangerous cargo. 

Kantarci is also getting insights into how Alzheimer’s may take hold once oral bacteria are in the brain. In a second study, he and his colleagues gave mice gum disease, observed how the bacteria migrated to the rodents’ brains and then measured how the numbers of various cells in the brain changed. Their key finding involved a type of immune cell called microglia, many more of which were activated when the bacteria appeared in the brain.

Microglia act as first responders, destroying invading pathogens and sending out chemical signals that summon other immune cells to join the fight. They are also responsible for destroying beta-amyloid plaques. So, in the brains of such people, microglia are already working double time.  

Kantarci thinks that, when the oral bacteria arrive, they tip the already overextended microglia over the edge and kick off a snowball effect of inflammation. Scientists already suspect that inflammation might be the underlying cause of Alzheimer’s disease. In that view, the oral bacteria might bean other contributing factor, perhaps the straw that breaks the camel’s back. 

Gut health

Bacteria from the mouth can migrate and wreak havoc in a range of other places too, including the gut. “Normally, if a healthy person swallows bacteria, they are either killed on the way down due to the acidity in the stomach or, once they get to the gut, there won’t be space for them because it’s already full of other bacteria,” says immunologist Joana Neves at King’s College London. However, she and others are starting to think that, if a person’s gut has an existing problem, that creates an opportunity for mouth microbes to move in. 

Take people with inflammatory bowel disease (IBD), a group of conditions in which the immune system attacks parts of the digestive system. One hypothesised explanation for IBD is that the gut lining is more oxygenated than usual, so the intestine is more accommodating to oral bacteria. There is evidence to support this: one study analysed the intestines of 39 people with IBD who were undergoing elective colon surgery and found that affected biopsy samples contained much higher levels of oral bacteria compared with nearby healthy colon tissue. In people with IBD, the gut lining could be leaky, enabling oral bacteria to get into the blood. This would then make the immune system go bananas and result in the gut attacking itself. There is already evidence from studies in mice that indicates this might be the case. 

In the case of Alzheimer’s and IBD, then, we can think of oral bacteria as acritical factor that lowers the threshold at which an existing condition becomes problematic. For other conditions, though, some scientists believe oral bacteria can act as the cause.

Heart disease 

Cardiologist Ntobeko Ntusi at the University of Cape Town in South Africa leads a team looking at the causes of atherosclerotic heart disease, in which fat and cholesterol build up in the arteries. This build-up, called plaque, blocks blood vessels and can cause a heart attack or stroke. Ntusi has found a strong link between disease se-verity and the type of bacteria a person has living in their mouth. And he isn’t alone. Another study tracked more than10,000 healthy volunteers over 15 years and showed that participants with gum disease were more than twice as likely to go on to have a stroke as people without the condition. Meanwhile, a separate analysis showed that gum disease and tooth loss increased the risk of coronary artery disease by 24 and 34 percent, respectively.  

This time, there is good evidence that oral bacteria are the direct culprit. In 2011, a team led by periodontologist Elena Figuero at the Complutense University of Madrid scraped plaque from the carotid arteries of people with heart disease and sequenced the bacterial DNA in it. The researchers found bacteria traditionally associated with gum disease in the plaque, including P. gingivalis. It seems that the oral bacteria are migrating to the arteries and settling down there. “Theyare very good at producing a protective layer of biofilm, which protects them from antibiotics and your own body’s mechanisms of defence,” says Ntusi. 

Once they have set up home, oral bacteria cause atherosclerosis by provoking immune cells to release chemical messengers called cytokines. Cytokines turn LDL cholesterol, otherwise known as ‘bad cholesterol’, into a special oxidised form that builds up on artery walls. Experiments in rodents and pigs have shown that even perfectly healthy animals can develop heart disease quickly if oral bacteria colonise their coronary arteries. 

Clearly, letting our oral microbiome go bad is deeply risky. It would be easy to feel gloomy about all this. After all, who outside of Hollywood has perfect pearly whites? Happily, though, looking after our teeth isn’t that difficult. Dentists recommend brushing your teeth with fluoride toothpaste twice a day and cleaning between them with floss or interdental brushes. 

Even if you develop gum disease, there are effective treatments that can reverse this, such as deep cleaning under the gums, where dentists use special instruments to scrape plaque, tartar and bacteria from below the gum line. Antibiotics, gum surgery or having some teeth removed are also options. Kantarci says there is no evidence that cosmetic procedures like teeth whitening or veneers will either significantly help or harm your oral microbiome. 

There may also be a way to protect yourself in advance. Dental scientist Eric Reynolds at the University of Melbourne, Australia, is developing a vaccine against gum disease. It works by getting the body to produce antibodies that detect and neutralise gingipains, those troublesome enzymes produced by P. gingivalis. In2016, the vaccine was tested in mice that had been infected with the bacterium, and it protected the ridge in which teeth sit from degradation. Reynolds is now planning human trials. 

Meanwhile, anthropologist Laura Weyrich at Penn State University has a more radical idea. It grew out of work she and her team have been doing over the past decade: studying plaque on the teeth of human remains from as far back as about 20,000 years ago through to the modern day. In general, the oral health of Neanderthals and ancient humans was excellent, she says. There are only a few known examples of cavities in Neanderthal teeth, and these come from places where they ate acorns, a relatively sugar-rich food. But they did still get a gunky build-up of plaque on their teeth, and Weyrich’s goal was to analyse the DNA in this to reconstruct a history of the human oral microbiome.

So far, she has found that the oral microbiome of our ancestors became markedly unhealthier after we switched from being hunter-gatherers to farmers about 8,000 years ago. At that time, “people drastically shifted their diet and started eating more carbohydrates, and that selected for the types of microbes that we associate with things like dental cavities,” says Weyrich. In unpublished work, she has since found that similar step changes in the oral microbiome occurred after the industrial revolution and the Second World War. 

Oral microbiome transplant 

Fascinating in themselves, these results also gave Weyrich an idea. Could we swap our bad, modern oral microbiome for the healthy version that ancient humans had? There would be a precedent for this, in the sense that faecal transplants are already used to help replenish the gut microbiome. For the oral equivalent, Weyrich envisages loading the bacteria into a device similar to a mouth guard that would be worn on the teeth for a short while, allowing the microbes to settle in the mouth. 

Working with Peter Zilm at the University of Adelaide in Australia and his colleagues, Weyrich has identified a suite of beneficial microbes found in the mouths of our ancestors, as well as those of healthy volunteers. “We know that there are people alive today who eat lots of sugar, never brush their teeth, never go to the dentist and yet miraculously have never had a dental cavity,” says Weyrich. “Those are the people who we’ve been recruiting as donors for oral microbiome transplantation.” 

Her team has conducted successful transplants in rats, but more work is needed before the technology can be applied to humans. One concern, for example, is that different populations of people have distinct oral biomes, so giving an Indigenous Australian person, for instance, a bacterium from a European might be ineffective or even harmful. There is also the question of how to grow the microbes that our ancestors had, many of which are no longer easy to come by. 

Weyrich says we simply don’t know what will happen if we take microbes that lived in the mouths of our ancestors and plonk them into a modern mouth – so we must proceed with caution. “It will be quite a puzzle to put it all together,” she says. “But it’s a puzzle we are really excited about tackling.”