Saliva/Pathogen Biomarker Signatures and Periodontal Disease Progression

Department of Periodontics and Oral Medicine, Michigan Center for Oral Health Research, University of Michigan School of Dentistry, 24 Frank Lloyd Wright Dr., Lobby M, Box 422, Ann Arbor, MI 48106 USA.
Journal of dental research (Impact Factor: 4.14). 03/2011; 90(6):752-8. DOI: 10.1177/0022034511399908
Source: PubMed


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 ( number, CT00277745).

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Available from: Christoph Andreas Ramseier, Jul 30, 2014
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    • "Two previous studies indicated that a combination of salivary biomarkers and subgingival plaque pathogens is associated with periodontitis and its progression more strongly than individual markers ( Ramseier et al . , 2009 ; Kinney et al . , 2011 ) . Moreover , the combination of the levels of three selected salivary biomarkers , namely MMP - 8 , IL - 1β , and P . gingivalis , was associated with periodontitis better than any of the markers alone ( Gursoy et al . , 2011 ; Salminen et al . , 2014 ) ."
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    ABSTRACT: Our aim was to investigate the value of salivary concentrations of four major periodontal pathogens and their combination in diagnostics of periodontitis. The Parogene study included 462 dentate subjects (mean age 62.9 ± 9.2 years) with coronary artery disease (CAD) diagnosis who underwent an extensive clinical and radiographic oral examination. Salivary levels of four major periodontal bacteria were measured by quantitative real-time PCR (qPCR). Median salivary concentrations of Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia, as well as the sum of the concentrations of the four bacteria, were higher in subjects with moderate to severe periodontitis compared to subjects with no to mild periodontitis. Median salivary Aggregatibacter actinomycetemcomitans concentrations did not differ significantly between the subjects with no to mild periodontitis and subjects with moderate to severe periodontitis. In logistic regression analysis adjusted for age, gender, diabetes, and the number of teeth and implants, high salivary concentrations of P. gingivalis, T. forsythia, and P. intermedia were significantly associated with moderate to severe periodontitis. When looking at different clinical and radiographic parameters of periodontitis, high concentrations of P. gingivalis and T. forsythia were significantly associated with the number of 4–5 mm periodontal pockets, ≥6 mm pockets, and alveolar bone loss (ABL). High level of T. forsythia was associated also with bleeding on probing (BOP). The combination of the four bacteria, i.e., the bacterial burden index, was associated with moderate to severe periodontitis with an odds ratio (OR) of 2.40 (95% CI 1.39–4.13). When A. actinomycetemcomitans was excluded from the combination of the bacteria, the OR was improved to 2.61 (95% CI 1.51–4.52). The highest OR 3.59 (95% CI 1.94–6.63) was achieved when P. intermedia was further excluded from the combination and only the levels of P. gingivalis and T. forsythia were used. Salivary diagnostics of periodontitis has potential especially in large-scale population studies and health promotion. The cumulative strategy appears to be useful in the analysis of salivary bacteria as markers of periodontitis.
    Frontiers in Cellular and Infection Microbiology 10/2015; 5. DOI:10.3389/fcimb.2015.00069 · 3.72 Impact Factor
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    • "colleagues observed in a cross-sectional study an augmented diagnostic ability of salivary biomarkers when combined with bacterial profiles on subjects with periodontal disease (Ramseier et al. 2009). Furthermore , a longitudinal periodontal diseasemonitoring study combined with a nontreatment phase was able to recognize clusters of host response biomarkers and pathogens highly associated with periodontal breakdown (Kinney et al. 2011). Ultimately, the potential of saliva and GCF were confirmed to accurately identify periodontal disease activity and its response to non-surgical therapy (Kinney et al. 2014). "
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    ABSTRACT: Objectives: The aim of the present investigation was to determine the profile of peri-implant crevicular fluid (PICF) biomarkers combined with microbial profiles from implants with healthy peri-implant tissues and peri-implantitis to assess real-time disease activity. Material and methods: Sixty-eight patients were included in this cross-sectional study. They were divided into two groups: 34 patients with at least one healthy implant (control) and 34 with at least one peri-implantitis affected implant (test). Total DNA content and qPCR analysis for periodontal bacteria obtained from subgingival plaque samples (Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) and a PICF analysis for IL-1β, VEGF, MMP-8, TIMP-2, and OPG were performed. The individual and combined diagnostic ability of each biomarker for peri-implantitis and target bacterial species were analyzed. Results: The mean concentration of IL-1β (44.6 vs. 135.8 pg/ml; P < 0.001), TIMP-2 (5488.3 vs. 9771.8 pg/ml; P = 0.001), VEGF (59.1 vs. 129.0 pg/ml; P = 0.012), and OPG (66.5 vs. 111.7 pg/ml; P = 0.050) was increased in the peri-implantitis patients. The mean expression of MMP-8 (6029.2 vs. 5943.1 pg/ml; P = 0.454) and did not reveal a meaningful difference among groups. Total bacterial DNA of selected microorganisms was associated with a threefold or greater increase in peri-implantitis although no statistical significant difference. The ability to diagnose diseased sites was enhanced by T. denticola combined with IL-1β, VEGF, and TIMP-2 PICF levels. Conclusion: The present data suggest that the increased levels of the selected PICF-derived biomarkers of periodontal tissue inflammation, matrix degradation/regulation, and alveolar bone turnover/resorption combined with site-specific microbial profiles may be associated with peri-implantitis and could have potential as predictors of peri-implant diseases.
    Clinical Oral Implants Research 10/2015; DOI:10.1111/clr.12708 · 3.89 Impact Factor
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    • "Interestingly the power to predict differences between periodontal disease categories (moderate to severe periodontitis as compared to mild periodontitis and gingivitis) was increased when measures of salivary MMP-8 were combined with those of MMP-9, OPG, and calprotectin and quantification of periodontal pathogens such as P. gingivalis and Treponema denticola in dental plaque [82]. Also, a decline in the levels of MMP-8, MMP-9, OPG, and IL-1β occurred in parallel with changes in the levels of several periodontal pathogens in dental plaque [153]. Using hierarchical clustering analysis the authors found that the combined levels of biomarkers (both molecular and bacterial) successfully predicted progression of periodontitis and disease stability during the recovery phase for the majority of cases. "
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    ABSTRACT: Periodontitis is a chronic inflammatory condition of the tissues that surround and support the teeth and is initiated by inappropriate and excessive immune responses to bacteria in subgingival dental plaque leading to loss of the integrity of the periodontium, compromised tooth function, and eventually tooth loss. Periodontitis is an economically important disease as it is time-consuming and expensive to treat. Periodontitis has a worldwide prevalence of 5-15% and the prevalence of severe disease in western populations has increased in recent decades. Furthermore, periodontitis is more common in smokers, in obesity, in people with diabetes, and in heart disease patients although the pathogenic processes underpinning these links are, as yet, poorly understood. Diagnosis and monitoring of periodontitis rely on traditional clinical examinations which are inadequate to predict patient susceptibility, disease activity, and response to treatment. Studies of the immunopathogenesis of periodontitis and analysis of mediators in saliva have allowed the identification of many potentially useful biomarkers. Convenient measurement of these biomarkers using chairside analytical devices could form the basis for diagnostic tests which will aid the clinician and the patient in periodontitis management; this review will summarise this field and will identify the experimental, technical, and clinical issues that remain to be addressed before such tests can be implemented.
    04/2014; 2014:593151. DOI:10.1155/2014/593151
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