title: 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.
authors.affiliation: 1 Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan.|2 AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kuboniwa
authors.affiliation: 1 Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sakanaka
authors.affiliation: 1 Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan.|3 "Challenge to Intractable Oral Diseases" Project, Osaka University Dental Hospital, Suita, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Hashino
authors.affiliation: 4 Department of Biotechnology, Osaka University Graduate School of Engineering, Suita, Japan.|5 Division of Metabolomics, Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Bamba
authors.affiliation: 2 AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.|4 Department of Biotechnology, Osaka University Graduate School of Engineering, Suita, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Fukusaki
authors.affiliation: 1 Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Amano
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D057747:Periodontal Debridement; D010510:Periodontal Diseases / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D011237:Predictive Value of Tests; D012463:Saliva / Q000737:chemistry / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers
keywords: biomarkers; dental plaque; deriodontium; diagnosis; metabolomics; periodontal disease