The long term goal of our research is to develop a point-of-care (POC) diagnostic test to help clinicians identify sites and/or subjects that are susceptible to periodontal disease progression. The primary objective of this project is to identify biomarkers of periodontal disease progression. The central hypothesis is that a combination of host analytes and subgingival species will be effective as biomarkers of periodontal disease progression. Periodontal diseases are the most common cause of tooth loss among adults in the United States and recent studies suggested that they increase the risk for systemic conditions such as cardiovascular diseases, diabetes, respiratory diseases and can affect reproductive outcome. Further, periodontal diseases progress through bursts of activity followed by periods of quiescence. Early accurate identification of individuals and/or sites that are undergoing active disease progression is critical to signal the need for immediate intervention to minimize tooth loss, allow for proper allocation of resources to treat susceptible individuals, and limit the potential systemic sequelae of these infections. However, there are no practical clinical means of identifying periodontal sites and/or subjects that are progressing. Better biomarkers of periodontal disease activity are urgently needed to improve periodontal disease diagnosis, guide therapy, monitor activity, and evaluate treatment response.
Aim 1 will examine the longitudinal variability of levels of host biomarkers in GCF and saliva.
Aim 2 will examine the diagnostic utility of GCF and salivary levels of host biomarkers and uncultivated and cultivable taxa in saliva and in subgingival biofilm samples for discriminating progressing and non-progressing periodontal sites and subjects.
Aim 3 will determine the effects of periodontal therapy on the levels of salivary and GCF biomarkers and on uncultivated and cultivable taxa in saliva and in subgingival biofilms. Factors that strengthen this proposal include: 1) participation by two NIH Clinical and Translational Science Award centers (The Forsyth Institute and Michigan Center for Oral Health Research); 2) vast experience of both Centers in multiplex quantification of host biomarkers in oral fluids; 3) access to the newly developed RNA-oligonucleotide quantification technique (ROQT) for quantifying uncultivated and cultivable bacterial taxa; and 4) access to state-of-the-art bioinformatics cores to support analysis of large data sets. This project addresses the NIDCR's strategic interest in early detection and identification of risk factors for periodontal disease and reaffirms the center's commitment to facilitate the translation of science into clinical practice. Successful completion of this project will lead to validation of biomarkers that can be used in POC tests to help clinicians identify sites and subjects at risk for disease progression who require immediate intervention.

Public Health Relevance

Despite advances in our knowledge of the causes and risk factors associated with periodontitis, there are no signs of a decline in periodontal disease prevalence. In fact, longer retention of teeth, coupled with an aging population might account for future increases in the number of subjects affected by tooth loss due to periodontal destruction. The total expenditure on treating and preventing periodontal diseases is estimated in billions of dollars. At present there are no practical clinical means of establishing which periodontal sites or subjects are 'active'. The discovery of biomarkers of periodontal disease progression would provide clinicians with important information regarding the need for treatment, evaluation of treatment outcomes and prognosis for patients that could help improve preventive and therapeutic strategies.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project--Cooperative Agreements (U01)
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Oral, Dental and Craniofacial Sciences Study Section (ODCS)
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Atkinson, Jane C
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Forsyth Institute
United States
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Konig, Maximilian F; Giles, Jon T; Teles, Ricardo P et al. (2018) Response to comment on ""Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis"". Sci Transl Med 10:
Konig, Maximilian F; Abusleme, Loreto; Reinholdt, Jesper et al. (2016) Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med 8:369ra176
Teles, Ricardo; Benecha, Habtamu K; Preisser, John S et al. (2016) Modelling changes in clinical attachment loss to classify periodontal disease progression. J Clin Periodontol 43:426-34
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Yost, Susan; Duran-Pinedo, Ana E; Teles, Ricardo et al. (2015) Functional signatures of oral dysbiosis during periodontitis progression revealed by microbial metatranscriptome analysis. Genome Med 7:27
Duran-Pinedo, Ana E; Yost, Susan; Frias-Lopez, Jorge (2015) Small RNA Transcriptome of the Oral Microbiome during Periodontitis Progression. Appl Environ Microbiol 81:6688-99
Duran-Pinedo, Ana E; Chen, Tsute; Teles, Ricardo et al. (2014) Community-wide transcriptome of the oral microbiome in subjects with and without periodontitis. ISME J 8:1659-72
Teles, Ricardo; Teles, Flavia; Frias-Lopez, Jorge et al. (2013) Lessons learned and unlearned in periodontal microbiology. Periodontol 2000 62:95-162
Teles, F R; Teles, R P; Uzel, N G et al. (2012) Early microbial succession in redeveloping dental biofilms in periodontal health and disease. J Periodontal Res 47:95-104

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