The secrets of the oral microbiome

More than 700 species of bacteria live in our mouths. The mysteries of this ecosystem are now being unravelled.

Forward: features are independent pieces written for Mewburn Ellis discussing and celebrating the best of innovation and exploration from the scientific and entrepreneurial worlds.

Raul Bescos was intrigued.

He was researching the effect of exercise on the body and blood pressure.

In most of the participants in his study, blood pressure dropped after exercise as expected, but in a handful it failed to fall.

On questioning them, it emerged that most of the ‘non-responders’ were using antibacterial mouthwash.

Bescos, a physiologist at the University of Plymouth, wondered if there was a link. Was the use of mouthwash somehow stopping blood pressure from falling? And, if so, how was it doing it? Was it to do with the bacteria in the mouth?

While it might seem like an odd leap to make, scientists from Queen Mary University of London and the Karolinska Institutet had recently shown that oral bacteria appeared to play an important role the regulation of blood pressure.

Dr Raul Bescos,
Lecturer in Dietetics, University of Plymouth

In their 2013 study, they’d found that blood pressure increased while using antibacterial mouthwash. Levels of nitrite in the blood, meanwhile, fell.

This second observation was key. Nitric oxide, which is produced by the reduction of nitrite in the blood, is a well-known vasodilator – that is, it relaxes blood vessels and so lowers blood pressure.

Some oral bacteria are known to reduce nitrates to nitrite and it seemed the mouthwash was stopping these bacteria from working, leading to blood pressure rising.

Bescos wondered if something similar was occurring in the participants in his study. Was the mouthwash preventing blood pressure from falling after exercise? Nitric oxide wasn’t thought to be responsible for the reduction of blood pressure after exercise, but perhaps it was involved after all.

‘This caught my attention,’ says Bescos, who ten years on is still researching the oral microbiome. ‘It was the moment when I thought, OK, maybe we should be paying more attention to what happens in the oral cavity.’

Tiny tenants of the mouth

The oral microbiome – the billions of bacteria, viruses, fungi and protozoa that call our mouths home – is second only to the gut microbiome in terms of size and diversity.

More than 700 different species of bacteria can live in the mouth, with most of us having 100 to 200 species – and up to 100 billion bacteria in total.

That furry feeling you get when you run your tongue over your teeth after forgetting to brush them the night before? That’s a bacterial film growing over the surface of your teeth.

These tiny tenants don’t just cause dental decay and gum disease – they may also have a big effect on our general health, with studies linking them to everything from Alzheimer’s disease and diabetes to heart disease and strokes.

In some cases, it’s thought that the bacteria themselves are doing the damage; in others, it is believed that the inflammation associated with periodontitis – severe gum disease fuelled by bacteria – is to blame.

Take heart attacks. Numerous studies have found that people who have gum disease are at higher risk of having a heart attack than those with healthy gums. The increase in risk varies from study to study, but in some cases it’s as high as three-fold.

There are two main mechanisms through which oral bacteria are thought contribute to cardiovascular disease, according to Dr Martijn Verhulst, medical liaison manager at Sunstar, a Japanese healthcare company with a particular interest in the oral microbiome. Both routes involve atherosclerosis, in which inflammation feeds the development of atherosclerotic plaques, the fatty deposits that narrow the arteries in cardiovascular disease.

Dr Martijn Verhulst,
Medical Liaison Manager, Sunstar

‘Firstly, there is strong evidence that periodontal bacteria can enter the bloodstream and travel to other places in the body,’ explains Verhulst. ‘For example, they are found in the atherosclerotic plaque, where they likely worsen the underlying inflammatory processes.

‘The local inflammatory response to bacteria in the mouth also causes an increase in systemic inflammatory markers, again speeding up the process of atherosclerosis elsewhere in the body.’

Of course, an association is not the same as causation, and it is possible that the links between oral health and general health are simply due to shared risk factors. Smoking, for instance, increases the odds of both gum disease and heart disease.

We’d be unwise, however, to dismiss the importance of the oral microbiome, says Bescos, who adds that while much of the evidence is circumstantial, some of the connections between oral health and general health are compelling.

Links with blood pressure

Curious about the link between the oral microbiome and blood pressure, Bescos ran a follow-up study in which healthy men and women ran on a treadmill for 30 minutes on two occasions a week.

After one session they rinsed their mouth with an antibacterial mouthwash; after the other they used a placebo solution of mint-flavoured water. The randomised, double-blind design meant that neither the participants nor the researchers knew which was which.

The participants’ blood pressure and saliva samples were taken before and after exercise.

The focus was on a phenomenon called post-exercise hypotension, in which blood pressure drops significantly after strenuous exercise and then stays low for several hours

One hour after exercise, systolic blood pressure had fallen, as expected. However, it had dropped almost twice as much when rinsing with the placebo as when using the mouthwash. Two hours after exercise, systolic blood pressure was still lower than usual when the placebo rinse was used, but it had returned to normal when using mouthwash.

The study also revealed that when the participants rinsed with the placebo – but not with the mouthwash – levels of nitrite in their blood rose after exercise. This, says Bescos, indicates that oral bacteria play a key role in lowering blood pressure, at least after exercise.

Learning more about how oral bacteria influence blood pressure could lead to new ways of treating hypertension, a condition that affects around one in three adults in the UK and is responsible for more than half of heart attacks and strokes.

Around 15 or 16 species of nitrate-reducing bacteria have been identified in saliva so far and there are likely more to be discovered, says Bescos. In his latest trial, he is looking at whether a mouthwash made from propolis, the waxy material that bees use to seal their hives, can lower blood pressure by encouraging the growth of these bacteria.

Propolis was chosen because is rich in polyphenols, plant compounds that, in the gut at least, fuel the growth of nitrate-reducing bacteria. However, not all bacteria thrive in the presence of propolis and propolis has long been used in dentistry to kill oral pathogens, including the gum disease bacterium

Early results, say Bescos, show that blood pressure did fall after using the propolis mouthwash twice a day for a week. Further analysis of the data will show whether the mouthwash did indeed increase the number of nitrate-reducing bacteria in the mouth – or even make them more active.

With the oral microbiome potentially involved in dozens of health conditions, there is no shortage of work for Bescos and his colleagues in the University of Plymouth’s Oral Microbiome Research Group.

He hopes to start work on the links between the oral microbiome and Alzheimer’s disease and multiple sclerosis, and has just completed a study that concluded that oral bacteria may be an under-recognised cause of brain abscesses.

Dental health

At Newcastle University, professor of oral microbiology Nick Jakubovics has long been interested in dental plaque, the sticky film of bacteria on our teeth.

He’s trying to find ways to break down the matrix of sugars, proteins and DNA that bacteria secrete to help them stick to teeth. Around ten years ago, he discovered an enzyme called NucB. Made by a marine strain of the bacterium.

Professor Nick Jakubovics,
Professor of Oral Microbiology, Newcastle University

More recent research has shown that as plaque gets older, the DNA in the matrix changes in structure and becomes resistant to the NucB. The hunt is now on for other enzymes that will attack this more mature plaque and could be added to mouthwash to combat tooth decay and gum disease.

Jakubovics’s interest in the oral microbiome doesn’t end there. His other research includes looking at how e-cigarettes affect the oral microbiome and how this compares to normal cigarettes.

His previous work has included looking at whether the contents of the oral microbiome can provide early warning of diabetes.

‘The evidence for associations between oral disease and systemic diseases – wider health – is quite strong,’ says Jakubovics. ‘The associations may be partly driven by shared risk factors – for example, excess consumption of sugars would impact both tooth decay and diabetes.

‘Even so, oral disease does seem to increase the risk of a wide range of other non-communicable diseases and this should not be ignored.’

‘Our health is like a big jigsaw puzzle,’ adds dentist Dr Victoria Sampson, founder of the Health Society clinic in central London. ‘The mouth and the bacteria living inside it are a very important piece of that puzzle. We 100% need to pay more attention to the oral microbiome.’