Saliva/pathogen biomarker signatures and periodontal disease progression

Abstract

The purpose of this study was to determine the role of saliva-derived biomarkers and periodontal pathogens during periodontal disease progression (PDP). One hundred human participants were recruited into a 12-month investigation. They were seen bi-monthly for saliva and clinical measures and bi-annually for subtraction radiography, serum and plaque biofilm assessments. Saliva and serum were analyzed with protein arrays for 14 pro-inflammatory and bone turnover markers, while qPCR was used for detection of biofilm. A hierarchical clustering algorithm was used to group study participants based on clinical, microbiological, salivary/serum biomarkers, and PDP. Eighty-three individuals completed the six-month monitoring phase, with 39 [corrected] exhibiting PDP, while 44 [corrected] demonstrated stability. Participants assembled into three clusters based on periodontal pathogens, serum and salivary biomarkers. Cluster 1 members displayed high salivary biomarkers and biofilm; 71% [corrected] of these individuals were undergoing PDP. Cluster 2 members displayed low biofilm and biomarker levels; 76% [corrected] of these individuals were stable. Cluster 3 members were not discriminated by PDP status; however, cluster stratification followed groups 1 and 2 based on thresholds of salivary biomarkers and biofilm pathogens. The association of cluster membership to PDP was highly significant (p < 0.0007). [corrected] The use of salivary and biofilm biomarkers offers potential for the identification of PDP or stability (ClinicalTrials.gov number, CT00277745).

Trial registration: ClinicalTrials.gov NCT00277745.

Figures

Figure 1.

Study timeline and recruitment/enrollment activities of the study. (A) Study timeline. (B) The study population was stratified into four groups.

Figure 2.

Longitudinal plots of mean (± SD) clinical periodontal measures stratified by initial category of periodontal health. Compared with baseline, individuals in the mild and moderate/severe periodontitis groups showed significant mean PD reductions at 8, 10, and 12 mos; those in the gingivitis group had significant mean PD reductions at 8 and 10 mos (p

Figure 3.

Longitudinal plots of mean (± SD) salivary biomarker levels stratified by initial category of periodontal health. Compared with baseline, significant reductions in salivary MMP-8 were seen in the moderate/severe periodontitis group at 8, 10, and 12 mos; those in the healthy group showed significant increases in MMP-8 levels at 12 mos (p

Figure 4.

Barplots displaying three clusters based on levels of salivary biomarkers, biofilm, serum biomarkers, and clinical measures. Within each cluster, the number of participants undergoing disease progression (≥ 2 sites demonstrating > 2 mm of CAL loss over 6 mos) is indicated. Np = number of participants within each group experiencing disease progression. Ns = number of participants within each group without disease progression.