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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    • "This observation reinforces the concept that these bacterial species in general are not typically detected in saliva samples from orally healthy individuals. In the last decade, much attention has been given to saliva-based screening for biomarkers associated with oral health and disease12, and increased salivary levels of analytes such as TNF-α, IL-1β and MMP-8 has been reported in patients with periodontitis when compared to orally healthy individuals [11,35]. In line, at group level different salivary bacterial community profiles have been shown between patients with periodontitis, dental caries and orally healthy individuals21222324. "
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    ABSTRACT: Objectives: Saliva is a biological fluid suitable for biomarker analysis, and differences in the salivary microbiota in oral health and disease have been reported. For such comparative analyses, time of sampling is critical since the bacterial composition may vary throughout the day, i.e., diurnal variation. The purpose of this study is to compare the salivary microbiome over time to determine the optimal time for sampling. Design: Stimulated saliva samples were collected from 5 orally healthy individuals in 4 h intervals for 24 h, and collection was repeated 7 days later (number of samples per person, n = 12, total number of samples, n = 60). Salivary microbiota was analyzed using the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS), and statistical analysis was performed using the Kruskal-Wallis test with Benjamini-Hochberg's correction for multiple comparisons, cluster analysis, principal component analysis and correspondence analysis. Results: From a total of 60 saliva samples, 477 probe targets were collectively identified with a mean number of probes per sample of 207 (range: 153-307). Little or no variation in microbial profiles within subjects was observed over time. Conclusions: Although there was considerable variation between subjects, microbial profiles within subjects were stable throughout a 24 hour period and after 1 week. Since there is little or no evidence of diurnal variation of the salivary microbiome, time of sampling of saliva is not critical for perturbation or other microbial studies.
    Full-text · Article · Jan 2016 · PLoS ONE
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    • "Recently the advanced researches in molecular mechanisms in the pathogenesis of periodontitis have provided information about the specific biological pathways and biomolecules that could be used as biomarkers for risk assessment, diagnosis, and prognosis (Kinney et al., 2011). Obviously, most studies focused on markers that hold potential diagnostic significance relevant to three important biological phases of periodontal disease: inflammatory phase, connective-tissue degradation phase, and bone-turnover phase (Miller et al., 2010). "
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    ABSTRACT: The detection of salivary biomarkers has a potential application in early diagnosis and monitoring of periodontal inflammation. However, searching sensitive salivary biomarkers for periodontitis is still ongoing. Oxidative stress is supposed to play an important role in periodontitis progression and tissue destruction. In this cross-sectional study, we investigated total antioxidant capacity (TAC) and total oxidant status (TOS) in saliva of periodontitis patients compared to healthy controls and their relationship with periodontopathic bacteria and periodontal disease severity. Unstimulated saliva was collected from 45 patients with generalized severe periodontitis and 37 healthy individuals and the TAC/TOS were measured. In addition, salivary levels of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Fusobacterium nucleatum in saliva were measured. Salivary TAC was lower in periodontitis patients compared to healthy controls. Moreover, a significant negative correlation of salivary TAC with clinical attachment loss was observed in periodontitis patients. No significant difference in the salivary TOS was observed between periodontitis patients and healthy controls. Bacterial load was enhanced in periodontitis patients and exhibited correlation with periodontal disease severity but not with salivary TAC/TOS. Our data suggest that changes in antioxidant capacity in periodontitis patients are not associated with increased bacterial load and are probably due to a dysregulated immune response.
    Full-text · Article · Jan 2016 · Frontiers in Cellular and Infection Microbiology
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    • "A finding of clinical importance is that the pathogens in advanced periodontal and carious lesions were detected in the initial stages of the disease as well, suggesting that they can be suitable candidates for disease risk assessment. Since dental pathogens may also colonize healthy sites, assessment of periodontal and caries risk will require the addition of other risk markers—for example, host factors in periodontitis [24], and diet in dental caries [25]. "
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    ABSTRACT: Background: The Journal of Oral Biosciences is devoted to the advancement and dissemination of fundamental knowledge concerning every aspect of oral biosciences. Highlight: This review article features the following topics: "Novel challenge for bone formation and bone resorption," "The front line of research on oral microbiota," "Clinical insight into the study of orofacial pain," "Carving a disease by omics," "The front line of bioimaging-a new light shining on oral biosciences," "Biodental engineering-integration of biology and material science," "Translational dental research over the CCN family," "Salivary glands," "Break the negative spiral consisting of periodontitis, diabetes, and Alzheimer's disease: extending healthy life expectancy through oral health," "Immunology and oncology," "Oral microbiome and biofilm research: new concepts and new approaches," "Bone remodeling mechanisms of bone resorption and bone formation," and "The front line of oral biofilm research," in addition to review articles by invited authors in the field of microbiology. Conclusion: These reviews published in the Journal of Oral Biosciences have inspired the readers of the journal to broaden their knowledge regarding various aspects of oral biosciences. The current editorial review introduces these exciting review articles.
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