Title: Derivation and validation of microbe-associated-molecular-patterns-based biomarkers for personalised periodontal medicine
Funder: The Academy of Medical Sciences

Abstract: Hypothesis: Subgingival and salivary endotoxin activity (determined by the lipid A chemical composition and the amount of LPS) can be used as a reliable, bacterially-derived biomarker and a risk assessment tool for prevention of periodontal diseases and personalised periodontal care. The aim of this study is: - To develop and evaluate a quick, efficient and objective monitoring and diagnostic method, based on the subgingival and salivary Limulus Amoebocyte Lysate (LAL) assay, with the ability to screen for susceptibility to periodontal diseases, identify disease progression, evaluate response to treatment and predict future tissue destruction. The salivary test should be available to large numbers of people through retail and general sale and could be routinely used by general public for self-testing in order to monitor and improve their periodontal health. The subgingival test is for the use of dental care professionals for personalised, tooth-specific periodontal care. Objectives of the study are: 1. To determine subgingival and salivary lipid-A profiles in persons with healthy/ stable periodontium, patients with gingivitis and patients with periodontitis using Mass-spectrometry. 2. To measure endotoxin activity of saliva and subgingival plaque samples using the Recombinant Factor C (rFC) assay. 3. To assess the inflammatory potential of subgingival and salivary lipid-A extracts in a periodontal ligament cell model and to relate it to endotoxin activity. 4. To devise, optimise and evaluate a novel, rapid, convenient and reliable subgingival and salivary test for periodontal tissues destruction risk-assessment and patient stratification, based on the rFC assay.

Lay abstract: Periodontitis is an irreversible disease of the tissues supporting the teeth and is characterised by the alveolar bone resorption that ultimately leads to tooth loss. While much progress has been made in the last two decades in the treatment and the management of periodontal diseases, these conditions are still often diagnosed only after they become symptomatic and significant, irreversible destruction of teeth supporting structures has already occurred. This is a major drawback, since by then, the disease might have become partially or totally unresponsive to periodontal therapy. Late diagnosis of periodontitis is due to the lack of accurate, non-invasive indicators that would allow disease identification during the pre-clinical stage—as it is often done in many other medical conditions. The current diagnostic criteria are based on the detection of historic tissue destruction and leave no opportunity to predict future activity of the disease or to formulate the appropriate treatment plan specific to each individual patient. Our aim is to develop a rapid and reliable test based on oral bacterial lipid-A profile, which can be used routinely by the dental care professionals and the wider public in order to maintain and improve oral health and quality of life and to encourage access to dental care and reduce health disparities. The test would be made in two versions: 1) for home, self-testing for early detection and prevention of periodontal disease before significant tissue destruction occurs, and 2) for the chair-side use by dental professionals for personalised, point-of-care periodontal therapy.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL