The relationship between oral health and overall health has been a focus for research for some time, write Professor Iain Chapple and Professor Tariq Iqbal, with periodontal disease (PD) linked to 57 non-communicable diseases (NCDs), including diabetes, cardiovascular disease and rheumatoid arthritis.¹
The mouth is a gateway to the whole body. It is also unique in that teeth, unlike skin, do not shed. This means bacteria can build up on the surface of teeth and enter the body through the bloodstream and by swallowing saliva.
When this happens, periodontal bugs can prime and stimulate white blood cells within the blood stream, putting them in a state of ‘high alert’ and resulting in the release of damaging mediators called oxygen radicals and cytokines, which drive inflammation. Both periodontitis and inflammatory bowel disease (IBD) are characterised by inflammation in underlying tissues.
Our work explores the link between oral and gut health, particularly in relation to PD and IBD. Further research into the two-way relationship between the microbiomes and inflammation in the mouth and gut will lead to earlier diagnosis via analysis of molecular signatures in saliva, better differentiation between types of IBD and the development of novel targeted therapies.
Faecal microbiota transplantation (FMT) involves the transplanting of a healthy microbiome from a screened healthy individual into patients with disease and is the most powerful way of altering the gut microbiome. FMT is an established and successful treatment for managing Clostridium difficile (C. diff) colitis. Our pilot studies have shown that it can also be used to treat people living with ulcerative colitis – a form of IBD.
The Birmingham Microbiome Treatment Centre is the only Medicines and Healthcare products Regulatory Agency (MHRA) licensed centre in the UK. It’s also the most active in Europe. We also have an IBD inception cohort where newly referred patients are seen by both the gastroenterology team and dental surgeons, and additional large cohorts at risk of liver-gut damage and bowel cancer.
FMT is enabling us to restore balance in the gut microbiome. But as global leaders in FMT, we’re also able to use it as a powerful discovery tool to understand exactly which microbiome components are working to improve symptoms and gut health.
Knowing which bacteria is effective in FMT supports us in developing novel targeted biotherapeutics (reducing the need for medication). It also means we’re able to explore if healthier gut microbiomes affect microbiomes in the mouth and vice versa.
Biomarkers are like fingerprints and saliva is rich in biomarkers of both oral and overall health conditions. As a diagnostic tool, it’s also accessible, non-invasive, precise, and inexpensive.
Integrated analysis of saliva’s biomarkers will help us identify clusters of biomarkers and develop algorithms to detect IBD earlier and differentiate between IBD and irritable bowel syndrome (IBS), and ulcerative colitis and Chron’s disease. It could also identify early colorectal cancer risk and even in-situ lesions (abnormal cells that have not spread beyond where they first formed but have the potential to do so) and primary sclerosing cholangitis (PSC) IBD, a severe inflammatory condition affecting liver as well as the gut.
Using saliva in the management of IBD could reduce the number of invasive endoscopies and would provide a potential new tool to diagnose and monitor disease.
Our world-class sequencing expertise and bioinformatic experience will help us highlight both pathogens and missing healthy components of the gut microbiome to develop pathways to target with intervention. These interventions will be based on manipulating microbiome triggers through our established FMT programme as we begin to take first steps in oral microbiota transplantation (OMT).
Our aim is to improve diagnosis and prognosis and make more informed decisions on IBD treatment through biomarker discovery and implementation and by understanding more about how different microbiomes affect gut and oral immune responses.
Our Patient and Public Involvement and Engagement (PPIE) panels are at the heart of our work. Working together has enabled us to establish an IBD inception cohort. We have also built cohorts for Lynch syndrome (the most common cause of hereditary colorectal cancer) and primary sclerosing cholangitis (PSC) (where the liver’s bile ducts become inflamed and scarred).
PSC is just one example of other non-communicable diseases in which our work could make a difference. This liver condition has been linked to IBD and we’re currently undertaking FMT studies for it.
Our work in exploring the relationship between oral and gut health is helping us develop the next generation of gut microbiome manipulation. This will also inform the development of oral microbiome manipulation to manage PD.
Rather than looking at IBDs in terms of reacting to symptoms and damage limitation, we’re taking a more proactive and holistic approach. Our focus is on addressing the triggers of IBDs and finding ways to spot them earlier and more easily. Redressing immune-microbiome imbalance could help us improve patients’ quality of life and reduce the need for current treatments.
1. Monsarrat et al, 2016, 'Clinical research activity in periodontal medicine: a systemic mapping of trial registers'