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Although periodontitis is a bacterial disease, its multidimensional nature and its bacterial complexity have made it difficult to definitively prove that specific microorganisms initiate the disease process. The successful implantation of a rifampin-resistant strain of the putative periodontal pathogen Bacteroides gingivalis into the periodontal microbiota of monkeys (Macaca fascicularis) resulted in an increase in the systemic levels of antibody to the microorganism and rapid and significant bone loss.

SUMMARYCapture ELISAs with biotinylated monospecific antibodies were developed to detect both C-reactive protein (CRP) and haptoglobin (Hp) in serum of adult periodontitis (AP) patients and normal subjects. Each acute-phase reactant was significantly increased in serum from AP patients with CRP at 9 : 12 Ϯ 1 : 61 mg/l versus 2 : 17 Ϯ 0 : 41 mg/l (P < 0 : 001) and Hp at 3 : 68 Ϯ 0 : 37 g/l versus 1 : 12 Ϯ 0 : 78 g/l (P < 0 : 001). Assessment of clinical characteristics of the patients' periodontal disease indicated that CRP and Hp levels were significantly increased in patients with the most frequent disease active episodes (P < 0 : 02 and P < 0 : 001, respectively). Longitudinal examination of the Hp levels showed a significant decrease following scaling and root planing (3 . 68 versus 2 . 38 g/l; P < 0 : 01). After a 2-year administration of 50 mg/b.i.d. Flurbiprofen (a non-steroidal anti-inflammatory drug), significantly decreased Hp levels were noted (P < 0 : 005). CRP levels declined by 35-40% after 1-2 years of treatment with the drug (P < 0 : 05). The findings indicated that localized infections resulting in increased inflammation and tissue loss in the periodontium elicit systemic host changes manifest by increases in two acute-phase reactants. The conclusions are that either these molecules are formed locally and distributed to the serum, or these presumably localized infections impact upon the systemic components of the host protective responses.

One of the predominant polymicrobial infections of humans is expressed clinically as periodontal disease. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia have been strongly implicated as members of a pathogenic consortium in the etiology of adult periodontitis. In this study we hypothesized that P. gingivalis, T. denticola, and T. forsythia are synergistic in terms of virulence potential and induce chronic periodontal inflammation that leads to alveolar bone resorption in a polymicrobial infection in rats. Groups of rats were infected with either P. gingivalis, T. denticola, or T. forsythia in monomicrobial infections or with all three species in polymicrobial oral infections with or without Fusobacterium nucleatum. PCR analyses of oral microbial samples demonstrated that rats infected with one bacterium were orally colonized by each of the bacteria during the study interval, and increased serum immunoglobulin G (IgG) antibody levels substantiated the interaction of the host with the infecting bacteria. PCR analyses of the rats with polymicrobial infections demonstrated that most rats were infected with P. gingivalis, T. denticola, and T. forsythia as a consortium. Furthermore, all rats exhibited a significant increase in the level of IgG antibody to the polymicrobial consortium. Radiographic measurement of alveolar bone resorption showed that rats infected with the polymicrobial consortium with or without F. nucleatum exhibited significantly increased alveolar bone resorption compared to the resorption in uninfected control rats, as well as the resorption in rats infected with one of the microbes. These results documented that P. gingivalis, T. denticola, and T. forsythia not only exist as a consortium that is associated with chronic periodontitis but also exhibit synergistic virulence resulting in the immunoinflammatory bone resorption characteristic of periodontitis.

Background Chronic inflammation in periodontal disease has been suggested as a potential risk factor in Alzheimer’s disease. The purpose of this study was to examine serum antibody levels to bacteria of periodontal disease in participants who eventually converted to Alzheimer’s disease (AD) compared to the antibody levels in control subjects. Methods Serum from 158 participants in the BRAINS (Biologically Resilient Adults in Neurological Studies) research program at the University of Kentucky were analyzed for IgG antibody levels to 7 oral bacteria associated with periodontitis including: Aggregati-bacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, Tre-ponema denticola, Fusobacterium nucleatum, Tannerella forsythia, and Prevotella intermedia. All 158 participants were cognitively intact at baseline venous blood draw. Eighty one of the participants developed either mild-cognitive impairment (MCI) or Alz-heimer’s disease (AD) or both, and 77 controls remained cognitively intact in the years of follow up. Antibody levels were compared between controls and AD subjects at baseline draw and after conversion and controls and MCI subjects at baseline draw and after conversion using the Wilcoxon rank-sum test. AD and MCI participants were not directly compared. Linear regression models were used to adjust for potential confounding. Results Antibody levels to F. nucleatum and P. intermedia, were significantly increased (α = 0.05) at baseline serum draw in the AD patients compared to controls. These results remained significant when controlling for baseline age, Mini-Mental State Exam (MMSE) score and apolipoprotein epsilon 4 (APOE ε4) status. Conclusions This study provides initial data that demonstrate elevated antibodies to periodontal disease bacteria in subjects years prior cognitive impairment and suggests that periodontal disease could potentially contribute to the risk of AD onset/progression. Additional cohort studies profiling oral clinical presentation with systemic response and AD and prospective studies to evaluate any cause-and-effect association are warranted.

Salivary diagnostics is an emerging field that has progressed through several important developments in the past decade, including the publication of the human salivary proteome and the infusion of federal funds to integrate nanotechnologies and microfluidic engineering concepts into developing compact point-of-care devices for rapid analysis of this secretion. In this article, we discuss some of these developments and their relevance to the prognosis, diagnosis and management of periodontitis, as an oral target, and cardiovascular disease, as a systemic example for the potential of these biodiagnostics. Our findings suggest that several biomarkers are associated with distinct biological stages of these diseases and demonstrate promise as practical biomarkers in identifying and managing periodontal disease, and acute myocardial infarction. The majority of these studies have progressed through biomarker discovery, with the identified molecules requiring more robust clinical studies to enable substantive validation for disease diagnosis. It is predicted that with continued advances in this field the use of a combination of biomarkers in multiplex panels is likely to yield accurate screening tools for these diagnoses in the near future. Keywordsacute myocardial infarction; lab-on-a-chip; periodontitis; salivary diagnosis Overview of the field of salivary diagnosisThe analysis of blood and its components has been the mainstay for laboratory diagnostic procedures for several decades. However, other biological fluids are also utilized frequently for the diagnosis of disease, for example urine and cerebrospinal fluid, and thus, saliva could offer some distinct advantages in select situations [1][2][3][4][5][6]. Saliva is a hypotonic fluid NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript composed mostly of water, electrolytes and organic molecules (i.e., amino acids, proteins and lipids). The water component is derived largely from the local capillary bed via intracellular diffusion, aquaporin water channels and extracellular routes [7,8]. Small neutral molecules from the serum enter by passive diffusion from the dense beds of capillaries surrounding and bathing the salivary glands. Electrolytes enter the saliva via osmotic gradients and are regulated by the rate of secretion, nature of the stimulus and level of mineralocorticoids in the circulation. The organic components of glandular saliva are derived largely from protein synthesis and are stored as granules within the acinar cells [4]. Because serum components of saliva are derived primarily from the local vasculature that originates from the carotid arteries [9], saliva has a prodigious fluid source that provides many, if not most, of the same molecules found in the systemic circulation. This makes saliva a potentially valuable fluid for the diagnosis of various systemic diseases (Figure 1).The recent cataloguing of the salivary proteome has availed considerable information that is potentially important for diagnostic applications ...

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