Use of saliva in diagnosis of Periodontitis: cumulative use of bacterial and host-derived biomarkers

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Background

The term periodontal disease usually refers to a group of infection-induced inflammatory diseases, affecting gingiva, connective tissue, periodontal ligament, and surrounding bone, that are caused by pathogenic microorganisms present in subgingival biofilm. Traditionally, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola have been considered as key organisms of periodontitis, and also Campylobacter rectus, Fusobacterium nucleatum, and Prevotella intermedia are common species in periodontitis. With the increase in bacterial numbers and their virulence factors, local inflammatory reaction activates the immune system. To activate the immune system, host tissues should recognize the shift in bacterial ecosystem and discriminate commensal and pathogenic bacteria from each other.
The recognition of bacteria and bacterial by-products initiates initial inflammatory response, which is achieved by the secretion of proinflammatory cytokines from epithelial cells and fibroblasts. After their migration to inflamed tissues, leukocytes suppress the bacterial invasion by their oxygen-dependent or -independent mechanisms. Subsequently, T- and B-cells emerge to the sites of infection and secrete immunoglobulins as an antigen-specific response. While the host defense mechanisms try to suppress the level of infection by eliminating the pathogens, the increased expression of proinflammatory cytokines, such as interleukin (IL)-1, -6, -11, and -17, and tumor necrosis factor (TNF)-α, stimulates the bone resorption. These cytokines can induce osteoclastogenesis by increasing the expression of Receptor Activator for Nuclear Factor κB Ligand (RANKL) and decreasing the osteoprotegerin (OPG) production by osteoblasts/stromal cells. Matrix metalloproteinases (MMPs), especially MMP-8 and -13, contribute to the bone tissue resorption.
The ability to monitor the health status, disease onset and progression, and treatment outcome through noninvasive means is the most desirable goal in health care promotion and delivery. As an easily collected and noninvasive specimen, saliva has been used as a diagnostic fluid in medicine. General aims in periodontal research on salivary diagnostics are to find marker(s) that could be used, preferably as chair-side tests, for example, to determine the activity of periodontitis or the outcome of the treatment, or, to a lesser extent, to detect periodontitis in field studies. Periodontitis is an infection-induced inflammatory disease with periods of exacerbations and remissions, thus, the fluctuation in disease progression clearly affects the diagnostic power of the salivary biomarker selected. This is also the case concerning some general diseases, such as diabetes, that deteriorate the periodontal disease progression and, at the same time, may affect the reliability of selected biomarkers. To overcome these limitations in salivary diagnostics, it would be beneficial to detect bacterial and host-derived biomarkers simultaneously. The cumulative use of bacterial and host-derived biomarkers greatly improve the development of simple methods for diagnosing different stages of periodontal disease in saliva. This does not only help researchers, involved in population-based studies, but also clinicians in estimating special care needs for their patients.

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