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.

The increased prevalence and severity of periodontal disease have long been associated with aging, such that this oral condition affects the majority of the adult population over 50 years of age. Although the immune system is a critical component for maintaining health, aging can be characterized by quantitative and qualitative modifications of the immune system. This process, termed 'immunosenescence', is a progressive modification of the immune system that leads to greater susceptibility to infections, neoplasia and autoimmunity, presumably reflecting the prolonged antigenic stimulation and/or stress responses that occur across the lifespan. Interestingly, the global reduction in the host capability to respond effectively to these challenges is coupled with a progressive increase in the general proinflammatory status, termed 'inflammaging'. Consistent with the definition of immunosenescence, it has been suggested that the cumulative effect of prolonged exposure of the periodontium to microbial challenge is, at least in part, a contributor to the effects of aging on these tissues. Thus, it has also been hypothesized that alterations in the function of resident immune and nonimmune cells of the periodontium contribute to the expression of inflammaging in periodontal disease. Although the majority of aging research has focused on the adaptive immune response, it is becoming increasingly clear that the innate immune compartment is also highly affected by aging. Thus, the phenomenon of immunosenescence and inflammaging, expressed as age-associated changes within the periodontium, needs to be more fully understood in this era of precision and personalized medicine and dentistry.

Background Salivary biomarkers of periodontitis were assessed longitudinally to determine response to therapy. Methods A 6-month case-controlled study of adults with chronic periodontitis was performed, with 33 participants receiving oral hygiene instructions (OHI) alone and 35 with scaling and root planing (SRP) combined with OHI. Saliva samples collected at week 0, 16 and 28 were analyzed for interleukin-1β (IL-1β), IL-8, macrophage inflammatory protein (MIP)-1α, matrix metalloproteinase-8 (MMP-8), osteoprotegerin (OPG) and tumor necrosis factor-α (TNF)-α. Clinical measures of periodontal disease were recorded at each visit. Results All parameters of periodontal health improved significantly in both groups by week 16 (p<0.0001) with the SRP group demonstrating greater benefit at week 16 and 28. Baseline OPG and TNF-α levels changed significantly at both follow-up visits (p<0.03), regardless of treatment group. IL-1β and MMP-8 levels decreased significantly from baseline (p≤0.04) in the SRP group only. OPG, MMP-8 and MIP-1α were significantly reduced in responders compared with non-responders (p=0.04, 0.01, 0.05 respectively). In receiver operating characteristic analyses, MMP-8 produced the highest area under the curve (≥ 0.7; p=0.01). Conclusion Salivary levels of IL-1β, MMP-8, OPG and MIP-1α reflected disease severity and response to therapy suggesting their potential utility for monitoring periodontal disease status.

Salivary biomarker discovery requires identification of analytes with high discriminatory capacity to distinguish disease from health, including day-to-day variations that occur in analyte levels. In this study, seven biomarkers associated with inflammatory and tissue destructive processes of periodontal disease were investigated. In a prospective cohort study design, analyte expression levels were determined in unstimulated whole saliva samples collected on multiple occasions from 30 healthy adults (i.e., orally and systemically) and 50 chronic adult periodontitis patients. Salivary levels of IL-1β, IL-6, MMP-8, and albumin were significantly elevated (5.4 to 12.6×) and levels of IFNα were consistently lower (8.7×) in periodontitis patients compared with the daily variation observed in healthy adults. ROC analyses of IL-1β, IL-6 and MMP-8 yielded areas under the curves of 0.963-0.984 for discriminating periodontitis from health. These results demonstrate that levels of salivary bioanalytes of patients who have periodontitis are uniquely different from normal levels found in healthy subjects, and a panel consisting of IL-1β, MMP-8 and IL-6 shows particular diagnostic potential.