Prediction of Periodontal Inflammation via Metabolic Profiling of Saliva

Abstract

Periodontal disease is characterized by chronic inflammation in subgingival areas, where a vast array of inflammation-associated metabolites are likely produced from tissue breakdown, increased vascular permeability, and microbial metabolism and then eventually show a steady flow into saliva. Thus, prolonged periodontal inflammation is a key feature of disease activity. Although salivary metabolomics has drawn attention for its potential use in diagnosis of periodontal disease, few authors have used that to investigate periodontal inflammation detection. In this pilot study, the authors explored the use of salivary metabolites to reflect periodontal inflammation severity with a recently proposed parameter-periodontal inflamed surface area (PISA)-used to quantify the periodontal inflammatory burden of individual patients with high accuracy. Following PISA determination, whole saliva samples were collected from 19 subjects before and after removal of supragingival plaque and calculus (debridement) with an ultrasonic scaler to assess the influence of the procedure on salivary metabolic profiles. Metabolic profiling of saliva was performed with gas chromatography coupled to time-of-flight mass spectrometry, followed by multivariate regression analysis with orthogonal projections to latent structures (OPLS) to investigate the relationship between PISA and salivary metabolic profiles. Sixty-three metabolites were identified. OPLS analysis showed that postdebridement saliva provided a more refined model for prediction of PISA than did predebridement samples, which indicated that debridement may improve detection of metabolites eluted from subgingival areas in saliva, thus more accurately reflecting the pathophysiology of periodontitis. Based on the variable importance in the projection values obtained via OPLS, 8 metabolites were identified as potential indicators of periodontal inflammation, of which the combination of cadaverine, 5-oxoproline, and histidine yielded satisfactory accuracy (area under the curve = 0.881) for diagnosis of periodontitis. The authors' findings identified potential biomarkers that may be useful for reflecting the severity of periodontal inflammation as part of monitoring disease activity in periodontitis patients.

Analysis of metabolic profiles of generalized aggressive periodontitis

“…In previous studies, saliva, serum and gingival cervical fluid were confirmed to demonstrate molecular changes during the development of chronic periodontitis. Many metabolites associated with inflammation, oxidative stress, tissue degradation and bacterial metabolism were found significantly elevated in periodontal disease …”

Analysis of salivary phenotypes of generalized aggressive and chronic periodontitis through nuclear magnetic resonance‐based metabolomics

“…They could be essential constituent of the patient unique saliva, they could derive from the breakdown of the host tissues as from the bacterial communities, even from the supragingival plaque. Kuboniwa et al . performed supragingival scaling prior to sample collection and found that the discriminating ability of their model was significantly improved.…”

“…They could be essential constituent of the patient unique saliva, they could derive from the breakdown of the host tissues as from the bacterial communities, even from the supragingival plaque. Kuboniwa et al 22 performed supragingival scaling prior to sample collection and found that the discriminating ability of their model was significantly improved. Also, in this study, a scaling session was not performed; being able to find differences in a largely noisy environment could have more impact on the development of a rapid, noninvasive diagnostic tool.…”

Host‐microbe interactions: Profiles in the transcriptome, the proteome, and the metabolome

“…Recent efforts have been made to understand the contribution of bacterial metabolism to the salivary metabolic profile in periodontal disease. Salivary metabolomics was utilized to characterize the periodontal disease status in the presence and the absence of supragingival plaque using a pre‐ and postdebridement approach and gas chromatography‐mass spectrometry . Metabolites associated with periodontal inflammation included ornithine, 5‐oxoproline, valine, proline, spermidine, hydrocinnamate, histidine, and cadaverine.…”

“…Salivary metabolomics was utilized to characterize the periodontal disease status in the presence and the absence of supragingival plaque using a pre-and postdebridement approach and gas chromatography-mass spectrometry. 101 Metabolites associated with periodontal inflammation included ornithine, 5-oxoproline, valine, proline, spermidine, hydrocinnamate, histidine, and cadaverine. Following debridement, a significant decrease in cadaverine was observed, as well as decreasing trends for ornithine, spermidine, and 5-oxoproline.…”