Project description:Onset of chronic periodontitis is associated with an aberrant polymicrobial community, termed dysbiosis. Findings of a recent model of its etiology suggested that dysbiosis holds a conserved metabolic signature as an emergent property. The purpose of this study was to identify robust biomarkers for periodontal inflammation severity. Furthermore, we investigated disease-associated metabolic signatures of periodontal microbiota using a salivary metabolomics approach. Collection of whole saliva samples was performed before and after removal of supragingival plaque (debridement). Periodontal inflamed surface area (PISA) was employed as an indicator of periodontal inflammatory status. Based on multivariate analyses using pre-debridement salivary metabolomics data, we found that the metabolites associated with higher PISA included cadaverine and hydrocinnamate, while uric acid and ethanolamine were associated with lower PISA. Next, we focused on dental plaque metabolic byproducts by selecting significantly decreased salivary metabolites following debridement. Metabolite set enrichment analysis revealed that polyamine metabolism, arginine and proline metabolism, butyric acid metabolism, and lysine degradation were distinctive metabolic signatures of dental plaque in the high PISA group, which may have relevance to the metabolic signatures of disease-associated communities. Collectively, our findings identified potential biomarkers of periodontal inflammatory status, while they also provide insight into metabolic signatures of dysbiotic communities.
Project description:Periodontal infections have been associated with systemic inflammation and risk for atherosclerosis and vascular disease. We investigated the effects of comprehensive periodontal therapy on gene expression of peripheral blood monocytes. Approximately 1/3 of the patients showed substantial changes in expression in genes relevant to innate immunity, apoptosis, and cell signaling. We concluded that periodontal therapy may alter monocytic gene expression in a manner consistent with a systemic anti-inflammatory effect. Experiment Overall Design: Fifteen patients with periodontitis contributed with blood samples at four time points: 1 week prior to periodontal treatment (#1), at treatment initiation (baseline, #2), 6 weeks (#3) and 10 weeks post-baseline (#4). At baseline and 10 weeks, periodontal status was recorded and subgingival plaque samples were collected and processed by checkerboard DNA-DNA hybridization. Periodontal therapy, including periodontal surgery and extractions but no adjunctive antibiotics, was completed within 6 weeks. At each of the four time points, serum concentrations of 19 biomarkers were determined using multiplex assays for Luminex technology. Peripheral blood monocytes were purified, RNA was extracted, reverse-transcribed, labeled, and hybridized with Affymetrix U133 Plus 2.0 chips. Expression profiles were analyzed using linear random effects models. Further analysis of Gene Ontology (GO) terms summarized the expression patterns into biologically relevant categories. Treatment resulted in substantial improvement in clinical periodontal status and reduction in levels of several periodontal pathogens. Expression profiling over time revealed more than 11,000 probes sets differentially expressed at a false discovery rate of <0.05.
Project description:Periodontal health, disease, and reoslution are characterized by a diverse cellular immune response in the oral mucosa. We used scRNAseq to robustly characterize the imme cell repertoire and asosciated changes across changes of conditions of health and disease.