Periodontitis is an inflammatory condition of the supporting tooth structures that results from the interaction of pathogenic subgingival communities with the host. The pathophysiology of this condition is not completely understood and thus the development of novel preventive or therapeutic strategies remains elusive. Microbial communities are complex dynamic entities in which microorganisms interact with each other, therefore displaying different phenotypic characteristics than individual species. Moreover, a community context modifies the pathogenic potential of microorganisms, which is realized not only by their direct interaction with host tissues but also indirectly by modulating the behavior of the whole community. Therefore, understanding the etiology of periodontitis requires considering microbial communities as the infectious challenge rather than focusing on single species as causative agents. Community models that approximate the taxonomic complexity, environmental conditions and growth rate of microorganisms in the subgingival environment are not available. Such models are necessary to investigate the inter-species interactions that support pathogenic communities. Moreover, animal models of periodontitis are required in which the pathogenic potential of human-like communities could be investigated. In this proposal, we will use recently acquired knowledge on the microbiome composition of humans with periodontitis to develop a 20-species model subgingival community. This model will be developed under continuous culture in nutritional and environmental conditions similar to those in vivo. Using this community model we will investigate inter-species interactions important for the survival of periodontitis-associated species. In particular, we will test the role of a group called "subgingival core species" which are important components of communities in health and disease and potentially serve as community metabolic anchors by supporting periodontitis-associated taxa. We will then evaluate the colonization and pathogenicity of the model 20-species community in the murine oral cavity, testing the hypothesis that microorganisms growing as a community and pre-adapted to environmental pressures such as oxygen are better able to colonize and induce periodontitis than single species. Accordingly, the specific aims of this proposal are: 1) To develop and characterize a chemostat-based subgingival community model representative of periodontitis and test the role of core species as fundamental for the survival of periodontitis- associated community members and 2) To develop a community-based oral gavage murine model of periodontitis. The models proposed will have great impact in the field as they will allow research on the pathogenesis of periodontitis to move beyond the study of single species, thereby facilitating identification of key events that modulate the establishment of pathogenic communities and their effects on host tissues. This knowledge is likely to direct the development of new strategies for preservation of periodontal health.

Public Health Relevance

This project will develop research models that will improve our understanding of the events that regulate the growth of the microbial communities associated with periodontitis (gum disease). The models developed will also help clarify the mechanisms by which these communities of bacteria cause disease. The results will likely help in the identification of novel strategies to prevent and treat periodontitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DE023967-01
Application #
8623646
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2014-06-01
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$220,800
Indirect Cost
$70,800
Name
University of Connecticut
Department
Dentistry
Type
Schools of Dentistry
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030