Panagakos Fs

Global Metabolomic Analysis of Human Saliva and Plasma from Healthy and Diabetic Subjects, with and without Periodontal Disease

Recent studies suggest that periodontal disease and type 2 diabetes mellitus are bi-directionally associated. Identification of a molecular signature for periodontitis using unbiased metabolic profiling could allow identification of biomarkers to assist in the diagnosis and monitoring of both diabetes and periodontal disease. This cross-sectional study identified plasma and salivary metabolic products associated with periodontitis and/or diabetes in order to discover biomarkers that may differentiate or demonstrate an interaction of these diseases. Saliva and plasma samples were analyzed from 161 diabetic and non-diabetic human subjects with a healthy periodontium, gingivitis and periodontitis. Metabolite profiling was performed using Metabolons platform technology. A total of 772 metabolites were found in plasma and 475 in saliva. Diabetics had significantly higher levels of glucose and α-hydroxybutyrate, the established markers of diabetes, for all periodontal groups of subjects. Comparison of healthy, gingivitis and periodontitis saliva samples within the non-diabetic group confirmed findings from previous studies that included increased levels of markers of cellular energetic stress, increased purine degradation and glutathione metabolism through increased levels of oxidized glutathione and cysteine-glutathione disulfide, markers of oxidative stress, including increased purine degradation metabolites (e.g. guanosine and inosine), increased amino acid levels suggesting protein degradation, and increased ω-3 (docosapentaenoate) and ω-6 fatty acid (linoleate and arachidonate) signatures. Differences in saliva between diabetic and non-diabetic cohorts showed altered signatures of carbohydrate, lipid and oxidative stress exist in the diabetic samples. Global untargeted metabolic profiling of human saliva in diabetics replicated the metabolite signature of periodontal disease progression in non-diabetic patients and revealed unique metabolic signatures associated with periodontal disease in diabetics. The metabolites identified in this study that discriminated the periodontal groups may be useful for developing diagnostics and therapeutics tailored to the diabetic population.

Clinical, Immune, and Microbiome Traits of Gingivitis and Peri-implant Mucositis

Tissues surrounding dental implants and teeth develop clinical inflammation in response to microbial stimuli. However, the literature suggests that differences exist in the microbial insult and inflammatory responses leading to gingivitis and peri-implant mucositis. In this pilot study, the authors use for the first time a systems biology approach to comprehensively evaluate clinical parameters, selected inflammatory markers, and the microbiome of subject-matched tooth and implant sites during native inflammation and in response to experimental plaque accumulation. Fifteen subjects with 2 posterior implants and corresponding contralateral teeth were examined at enrollment; at day 0, after reinstitution of gingival/mucosal health; at days 7, 14, and 21, during stent-mediated oral hygiene (OH) abstention; and at day 42, after resumption of OH. The subgingival microbiome was evaluated via 16S rRNA gene sequencing and 8 selected inflammatory markers measured in crevicular fluid. Comparison of teeth and implants via general linear models based on orthogonal polynomials showed similar responses in clinical parameters, inflammatory mediators, and proportions of individual microbial taxa during OH abstention. Implants, however, accumulated less plaque and underwent more heterogeneous shifts in microbiome structure. A multilevel, within-group, sparse partial least squares analysis of covariation of microbial, inflammatory, and clinical parameters throughout all study visits found inflammation around teeth and implants positively correlated with IL-1 alpha and IL-1 beta and with the proportions of Selenomonas, Prevotella, and 5 species-level phylotypes. Gingivitis, however, showed a stronger positive correlation with lactoferrin and IL-1ra and a stronger negative correlation with Rothia. Peri-implant mucositis, on the contrary, correlated positively with certain microbial taxa not associated with gingivitis by a previous study or the current one. In summary, differences existed between implants and tooth sites in microbiome evolution during OH abstention and in the correlation of specific inflammatory mediators and microbial taxa with clinical inflammation. Common biological features, however, were also identified for gingivitis and mucositis.

Type 1 Diabetes–associated TLR Responsiveness of Oral Epithelial Cells

In type 1 diabetes (T1D), a Toll-like receptor (TLR)-hyper-inflammatory monocytic phenotype has been implicated as a mechanism of exacerbated tissue destruction. Other cells of the periodontium, including oral epithelial cells (OECs), express innate immune receptors, including TLRs. To delineate the TLR responses of OECs derived from T1D participants and to determine effects of the anti-inflammatory agent triclosan on the TLR-hyper-inflammatory phenotype, primary human OECs from individuals with T1D and diabetes-free individuals were stimulated with TLR ligands in the presence and/or absence of triclosan. The expression of pro-inflammatory cytokines and micro-RNAs (miRNAs) was evaluated. While the repertoire of TLRs expressed by OECs is similar to that expressed by macrophages (Mϕ), the relative amounts and ratios are significantly different. OECs demonstrate a TLR-response profile similar to that of Mϕ, yet attenuated. OECs have a unique response to P. gingivalis LPS, where miR146a and miR155 play a regulatory role in responsiveness. OECs from T1D participants are TLR-hyper-responsive, due to dysregulated induction of miR146a and miR155, which is abrogated by pre-treatment with triclosan. The aberrant TLR-activation of OECs in T1D has the potential to contribute to excessive soft- and hard-tissue destruction. Importantly, triclosan’s anti-inflammatory property is effective in abrogating TLR-induced OEC hyperactivity.

Control of dentin/root sensitivity during non-surgical and surgical periodontal treatment

AIM To determine the efficacy of a desensitizing regimen compared to a control in preventing the occurrence and/or alleviating dentin/root sensitivity (DRS) following non-surgical (NSPT) and surgical periodontal treatment (SPT). METHODS Seventy-four chronic-periodontitis patients (CPP) were randomized into a test group (n = 38) using an in-office prophylaxis paste and a toothpaste at home both containing 8% arginine and calcium carbonate (Pro-Argin(™) Technology) or into a control group (n = 36) receiving a fluoride-free prophylaxis paste and a fluoride toothpaste. The examiner applied the assigned paste onto selected teeth for 3 s following NSPT and for 60 s before flap closure. Patients brushed with the assigned toothpaste twice daily throughout the study. DRS to air stimulus was assessed by the Schiff scale (0-3) and the Visual Analog Scale (VAS: 0-100 mm) six times over 17 weeks. RESULTS In the test group, VAS scores significantly decreased at 8, 11 and 17 weeks from baseline (p ≤ 0.003) and Schiff scores at 8 and 11 weeks from baseline (p ≤ 0.014). The control group exhibited significant increases in VAS and Schiff during the study period (p ≤ 0.006). Marked inter-group differences were noted at all time points (p < 0.001). CONCLUSIONS The combined use of desensitizing products (8% arginine and calcium carbonate) in-office and at-home prevented DRS development and maintained this effect for 17 weeks following NSPT and SPT.

Partners in Prevention: A Winning Approach for Communities and Companies

For years, dentistry as a profession has been solely focused on the treatment of disease. Patients would present with a dental problem and the dentist would address it, either through repair, replacement, or removal. In the late 19th and early 20th centuries, the closest the dental profession came to instituting a prevention approach to disease was during the focal infection era. During this period, perfectly sound teeth were extracted in young, healthy individuals to prevent the onset of a systemic disease, such as tuberculosis, arthritis, or heart disease. It was eventually recognized that this preventive measure had no impact on the eventual onset of these and other systemic diseases, and it was discontinued. It was not until the discovery of the caries-preventive effect of fluoride that a truly proactive approach to prevention was undertaken with success. Today, because of the consumption of fluoride through water sources, as well as daily use of fluoridated dentifrices, the rate of caries has decreased, although there are some early signs that some of the gains realized are reversing. In the United States, as well as other countries, implementation of water fluoridation was undertaken by public health authorities to provide people with protection from a preventable disease via a very efficient and effective route— the public water supply. In other parts of the world, fluoride is delivered by other sources, usually via dietary supplements. Fluoridation of dentifrices by oral health product manufacturers began in the early 1950s, with the first of these products using stannous fluoride as the fluoride source. Over the years, other forms of fluoride have been successfully delivered via a dentifrice, such as sodium fluoride, monofluorophosphate (MFP), and amine fluoride. Over the past 60 years, fluoride has been incorporated into many other vehicles for delivery to patients, either via over-the-counter products (mouth rinses, for example) or professionally applied/prescribed products, such as fluoride varnish, fluoride tablets, and traydelivered fluoride gels. Taken together, the impact on caries and the reduction in the caries rates among those with access to these sources cannot be argued. Today, with the level of fluoridated tap water consumption on the decline, these alternative delivery methods, especially