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Oral Health and the Connected Body

26 June 2015

Oral Health and the Connected Body

Some of Europe’s most influential Dental Professionals converged on Berlin for Philips’ 10th Oral Healthcare Symposium to learn more about the latest research and findings in oral health and systemic health.  These were presented by a number of the world’s leading authorities on the subject including five Professors - Robert J Genco from the USA; David Herrera from Spain; Philip Preshaw and Iain Chapple from the UK; Bruno Loos from the Netherlands; along with Dr Egija Zaura, an Associate Professor, also from the Netherlands.  By bringing together the best minds and leading innovators in one meeting the aim was to help shape the future of oral (and overall) health.

The overarching message of the symposium was that there is progressive evidence showing that the mouth is the gateway to the body for a number of destructive diseases (including cardiovascular disease, diabetes and rheumatoid arthritis.  There is a convergence of medical and oral health research pointing to the need for greater collaboration between medical and dental professionals (and companies such as Philips to help facilitate this by initiating and funding research as well as developing the health technologies to bring about meaningful advances in diagnosis and treatment).

Half the adult population has periodontitis

One of the foremost pioneers in the field Professor Robert J Genco is a Professor of Oral Biology, Microbiology and Immunology at The State University of New York at Buffalo.  It was Professor Genco’s 30 years conducting clinical research which established that smoking, diabetes mellitus, obesity, low dietary calcium, osteoporosis and stress are risk factors for periodontal infections.  Professor Genco stated that recent epidemiological studies have shown that periodontitis affects half the adult population, which is twice the prevalence formerly suggested.  

In his overview of periodontitis and systemic disease, Professor Genco explained that a chain reaction can be set up as a result of a localised periodontal inflammatory response which can in turn initiate localised inflammatory responses elsewhere in the body leading to multiple systemic responses.   These can include complications related to diabetes, heart disease, respiratory disease, cancer, adverse pregnancy outcomes, rheumatoid arthritis and has been shown to be implicated in Alzheimer’s disease.

Professor Genco explained that the organisms spread systemically as a result of sub gingival flora which travels through the bloodstream from the mouth to distant sites in the body. Studies of atheromatous plaques have shown that they harbour an entire microbiome rich in flora, including p.gigivalis, which originates from the mouth. 

This has wide ranging clinical significance including the potential to develop biomarkers to predict disease, the prescription of antibiotics and vaccines development.  It can also lead to the development of simple interventions, including improved oral hygiene, to help prevent fatal consequences of diseases.  In addition the use of anti-microbial agents could be introduced along with probiotics and prebiotics to change or affect the microbiome.  Future strategies will also need to be developed to attack the microbiome as it is travelling to reduce hematologic spread.

Fist sized area of ulcerated skin exposed to oral bacteria

To expand this theme Professor David Herrera discussed periodontitis and atherosclerotic cardiovascular disease and asked if bacteraemia provided an explanation. David Herrera is Professor of Periodontics and Associate Dean for Clinics at the Faculty of Odontology, University Complutense of Madrid.   

In a graphic demonstration Professor Herrera showed that a patient with periodontitis has inflamed and ulcerated epithelial surfaces within the gum akin to the dimensions of a clenched fist which is persistently exposed to live bacteria.  Studies have shown blood from the diseased mouth carries these oral bacteria around the body, and that dental procedures actually exacerbate this.   Interestingly, so do tooth brushing, flossing and the use of oral irrigators and tooth picks which makes the treatment part of the problem, however the worse the periodontal disease, the greater the bacteraemia, and so oral hygiene remains vitally important.

Professor Herrera explained that there is increased jeopardy of bacterial colonisation of other sites in the body including the heart (as well as the brain, the respiratory tract and the placenta) via blood from the month.  However, the most relevant consequences may not be colonisation of distant sites, but the increase of systemic inflammation.  As a result there is a significant risk of cardio vascular disease for people with periodontitis and as Professor Genco explained studies have shown the presence of periodontal bacteria at sites of atheroma.  It has been proven in vivo and in animal studies that such bacteria is able to invade and affect other types of cells, including endothelial cells in the blood vessels, and now more human evidence is needed to support this hypothesis.

The discussion moved from the heart to the reproductive system and focussed on the mother and new born infant. Dr Egija Zaura, an Associate Professor in oral microbial ecology at the Department of Preventive Dentistry at the Academic Centre for Dentistry in Amsterdam (ACTA) explained that our microbiome is crucial to help us digest food, fine tune the immune system and provide a natural defence against pathogens - it even communicates with the nervous system. In fact a ‘normal’ microflora evolves with us at different life stages, and changes as we age. 

A baby’s mode of delivery affects its microbiome

There are a number of ways that an infant acquires their oral microbiome; however it is primarily a vertical transfer from the mother to her infant which is directly affected by its mode of delivery - vaginal or caesarean section – and a baby which is delivered vaginally has a microbiome most akin to its mother’s.  At three months there are still significant differences between the microbiomes of babies born vaginally versus a C-section.  

Dr Zaura explained that there is a direct correlation between mothers with periodontitis and pregnancy complications and a cascade of reactions can be set up, resulting, at its worst, with premature or still birth.  During pregnancy a woman’s oral microbiome changes as a result hormone levels and this can result in swollen and bleeding gums which allow bacterial transfer from the mouth. Dr Zaura proposed a hypothesis that the placenta catches these oral bacteria and from there it trains the foetal immune system to recognise friend from foe:  once the baby is born it will recognise and tolerate oral bacteria from the mother.

If this hypothesis holds true and a baby’s immune system can be influenced in utero, this opens up the possibility to personalise pre-conceptual interventions, as well as offering pregnant women treatment strategies and pre and probiotics to ensure optimum oral health for both mother and child.

According to Professor Philip Preshaw, from Newcastle University in the UK, the longest standing and strongest evidence of a connection between periodontal and systemic disease is in diabetes, furthermore the connection is bi-directional.   Inflammatory mediators play a key role in bringing about periodontal inflammation in diabetes and are also likely to play a fundamental role in periodontal tissue destruction.  

Professor Preshaw explained that epidemiological studies have demonstrated that diabetes is a major risk factor for periodontitis and this is most worrying because 10 percent of adults worldwide – some 430 million people – and one in ten children are obese.  Obesity levels have doubled since 1980 and one in three Americans will develop diabetes, whilst in Europe half the population is obese and 52 million people have diabetes. Whilst the western world is currently bearing the brunt, developing countries are rapidly catching up.

Bi-directional connection and two way communications

There is evidence from a large number of studies that those with poorly controlled diabetes have a three-fold risk of developing periodontitis (and also have an increased probability of end-stage renal failure, nephrotic disease and cardiovascular disease).  According to Professor Preshaw treatment studies have suggested that effective periodontal therapy can result in improvements in glycaemic control – in fact a meta-analysis of studies shows a reduction of 0.4% in HbA1c (glycated haemoglobin, a measure of glycaemic control) can be achieved following periodontal treatment without drug intervention – which is equivalent to a second drug intervention in a diabetic regime. 

The role for the dental team is clear; studies show it is important to identify patients with risk factors for diabetes and offer them enhanced care including information on diet, nutrition, cholesterol control as well as oral health care advice.  They should also be guided to visit their doctor.  To underline the effectiveness of this style of intervention Professor Preshaw pointed to a study where 49 percent of the cohort of patients reported making significant beneficial lifestyle changes as a result of intervention by their dental professional.  In fact, patients were shown to be receptive to receiving information in the dental clinic and dental professionals enjoyed the enhanced role this presented them.  In his opinion this showed that there are multiple opportunities to educate and change both patients’ behaviour and that of medical colleagues. 

On being questioned Professor Preshaw expressed an opinion that saliva will play an increasingly important role in evaluating ‘at risk’ patients and will be fundamental in the future research and development of new diagnostic and treatment technologies.  He also felt that the potential for Philips to develop a probe to collect and crevicular fluid and identify biomarkers would be an incredibly powerful tool.

The symposium was also addressed by Professor Iain Chapple who is Head of Periodontology at Birmingham Dental School and Hospital who took as his theme the features and risk factors of a link between rheumatoid arthritis and periodontitis and questioned whether the relationship is coincidental or causal as both conditions are inflammatory diseases in which inflammation fails to resolve and host mediated tissue damage results.

Making the link

Rheumatoid Arthritis affects one percent of the population and is a chronic inflammatory condition which leads to structural damage including joint pain, swelling, stiffness and ultimately bone loss, damage, collapse and deformity.   There are undoubtedly parallels with periodontitis including inflammation and eventual bone loss. Some of the risk factors implicated in both conditions are also shared; however there are apparent differences in the pathogenesis of rheumatoid arthritis and periodontitis in that a microbial aetiology drives the periodontal inflammation whereas RA has a foundation in autoimmunity.  It has also been found, however, that bacteria may play a role in rheumatoid arthritis, just as periodontitis may have an auto immune component.   

80 percent of patients with inflammatory arthritis are seropositive and have markers which indicate the presence of anti-citrullinated protein antibody (ACPA) in their blood streams.  Interestingly the occurrence of these markers occurs 10 years before they develop signs and symptoms of the condition.  There is now a “two-hit” theory of RA pathogenesis, where the first hit may be by an infectious stimulus, which could be periodontitis. For example, p.gingivalis produces an enzyme which adds citrulline amino acids to proteins in the tissues, and such citrillunated proteins are the trigger for the generation of ACPAs….the antibodies that cause RA.  This leads to epitope spreading and auto immunity yet still no symptoms may show at this stage.  It is only when a “second hit” on the joints themselves occurs that it triggers the inflammatory joint process.  

Professor Chapple alluded to a study that set up an association between rheumatoid arthritis and periodontal disease which featured 4,461 participants over the age of 65.  This showed that the odds of patients with RA having periodontal disease were four time that of non-RA patients.

As with other conditions cited during the day of lectures, many risk factors of rheumatoid arthritis and periodontitis are shared including genetic predisposition and host mediation as well as smoking, socio-economic factors, a reaction to oxidated stress and female hormones.  Neutrophils are also implicated in both conditions.  There are also differences however, which in the case of periodontitis, include an infectious trigger and there is no qualified evidence yet that it is an auto immune disease.   Conversely with RA there is less evidence for an infectious trigger and it is an auto immune disease.

A hypothesis for a causal role for periodontitis in RA was proposed by Professor Chapple which flowed as follows:  periodontal inflammation is dominated by neutrophils and NETs are released along with citrullinated proteins…this is the “first hit”. p.gingivalis may also contribute to the citrullination. The citrullinated proteins generate antibodies (ACPAs). At a later point the second hit on the joint causes inflammation in the joint involving neutrophils that again release their NETs and citrullinated proteins. The ACPAs already generated by the first hit (periodontal disease) then cross-react with the citrullinated autoantigens from NETs in the joints and cause clinical signs of RA.

Joined up thinking

The symposium concluded with examples of Philips’ drive towards achieving superior oral and systemic health through innovation to improve people’s lives. Philips’ Principal Scientist Dr Marko de Jager explained that the Company’s vision of connected health is already being delivered by a variety of meaningful innovations from the development of the latest diagnostic, scanning and monitoring equipment to hospital information systems and even equipment which allows the visualisation of surgical procedures to provide more accurate surgery.

Philip’s health continuum approach includes technological advances to help with every aspect of healthy living from prevention to fast and accurate diagnosis, and then from treatment to recovery and home care, monitoring and a return to independent living. At-home healthcare is also a strong driving force, and Philips is responsible for developing clinically significant oral health devices and apps to encourage better brushing techniques and even defibrillation technology from which patients can benefit in a practice environment. Dr de Jager outlined some of the clinical research projects which are currently underway including one involving a consortium of some of the top academic institutions and companies including Wrigleys, Cargill, GSK and Philips.  Together they are looking for ways to help patients withstand or recover from oral health disease. 

Philips is also working on a five minute saliva diagnosis to identify biomarkers of periodontitis with two of the Professors who presented at the symposium - Philip Preshaw and Iain Chapple - to allow healthcare teams, including doctors and dental professionals, to identify and treat health-compromised patients.   For some people with a host of systemic health conditions, oral health problems are not the most important factors, but could be an important stepping stone in their diagnosis and treatment.

Philips’ vision is not only to facilitate learning but to connect healthcare professionals more effectively to collaborate in the diagnosis and care of their patients.  This is being realised with the development of connected healthcare systems and technologies which help patients adhere to recommend healthcare changes.  So there will be devices with sensors telling patients that they are living, sleeping or even tooth brushing efficiently, and giving feedback to their healthcare professionals or nudging them to make effective changes.  

Sharing the platform with Dr de Jager was Dr Marilyn Ward, who is Philip’s Director of Clinical and Dental Scientific Affairs who presented some of the latest clinical research from Philips Oral Healthcare supporting new product development.  This includes the launch of new power toothbrushes and heads, interdental cleaning devices, tooth whitening advances and products to address clean breath and halitosis.

According to Philips’ Senior Director Holger Kretschmer:

The retailing giant Amazon is predicting treble digit growth figures in the health and connectivity sector and is talking to health tech companies including Philips which have the knowledge and the products to bring this to fruition.  Few if any companies have the technological know-how to connect patients with healthcare providers in so many aspects of their lives and this is being accelerated to create joined up digital healthcare.”

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