Dental caries represents one of the most common chronic diseases affecting young children, and is a multi-factorial disease involving complex interactions of risk factors. The mutans streptococci (MS) group is among the most cariogenic microorganisms associated with dental caries. We propose to identify the microbial factors affecting the genetic diversity and potential selection of MS strains following caries restorative therapy in children. In prior work, we described genetic fingerprints of MS isolates (N=828) collected before and after treatment from children exhibiting severe early childhood caries (S-ECC). We have also identified the dominant MS genetic strains that occur in carious and non-carious sites within the oral cavity of individual patients (N=20), and have characterized strain cariogenicity properties. Our published studies have identified 39 MS genetic strains, and have found that caries restorative therapy in some patients results in population shifts to highly acidogenic or acid-tolerant MS strains, with single dominant MS strains appearing at 1-year post-therapy. The objectives of this current project are to initiate a new cohort of 250 patients where restorative and adjunctive therapy measures can be applied independently to ascertain selective effects, determine if MS genetic strains with distinct cariogenicity profiles undergo preferred selection in carious sites versus non-carious sites within the oral cavity of individual patients, and develop a standardized genetic database of MS variants with defined cariogenic phenotypes that may serve as predictive microbial identifiers for dental caries and treatment outcomes. The study hypothesis is that children with S-ECC may possess distinct genetic strains of MS, which undergo resistance and/or selection during specific aspects of caries restorative treatment, and this impact the effectiveness and long-term outcome of the treatment. The translational goal of this project will be to provide insight on the efficacy of restorative an adjunctive therapy practices in the elimination and/or reduction of certain MS genetic strains in caries-active children. The significance of this study is profound, as treatment in some patients with S-ECC results in the appearance of dominant and highly-cariogenic MS genetic strains, which conceivably could place the patient at even higher risk. This study is innovative because of its potential to predict the outcome of caries preventive therapy based on the identification of the MS genetic strains. The OHSU School of Dentistry is an eligible institution for an R15 AREA award. The Principal Investigator and collaborative faculty group have mentored over 13 graduate dental residents, 30 dental students and 18 undergraduate students in research over the past 5 years, and we anticipate continued success in the recruitment of new student researchers for the R15 award.

Public Health Relevance

The project relevance of this research is the potential impact on the standard-of-care practices for caries preventive therapy in children, with implications in defining the use of antimicrobial rinse and fluoride therapy in the oral health care of children in the United States. This research may result in shifts in clinical practice paradigms (e.g.: widespread use of specific antimicrobial rinses) for select patients and may lead to the development of personalized dentistry practices. Long-term translational goals, which may alter clinical practice in pediatric oral health, are to provide real-time prognosis of the effectivenessof caries preventive therapy at the initial point-of-care and to provide better assessment of treatment outcome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
3R15DE024317-01S1
Application #
9136362
Study Section
Special Emphasis Panel (ZRG1-MOSS-T (82))
Program Officer
Fischer, Dena
Project Start
2014-09-15
Project End
2017-08-31
Budget Start
2015-09-04
Budget End
2017-08-31
Support Year
1
Fiscal Year
2015
Total Cost
$100,000
Indirect Cost
$35,065
Name
Oregon Health and Science University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
George, Noelle; Flamiatos, Erin; Kawasaki, Kellie et al. (2016) Oral microbiota species in acute apical endodontic abscesses. J Oral Microbiol 8:30989
Gilbert, Kenneth; Joseph, Raphael; Vo, Alex et al. (2014) Children with severe early childhood caries: streptococci genetic strains within carious and white spot lesions. J Oral Microbiol 6: