{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:46:08Z","timestamp":1788997568454,"version":"build-2803163510"},"reference-count":71,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008978","name":"Philips Oral Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008978","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To explore the potential of metabolomic profiles of oral rinse samples to distinguish between patients with severe periodontitis (stage III\/IV) and non\u2010periodontitis controls. This is coupled to an analysis of differences in metabolomic profiles between individuals without periodontitis, patients with localized periodontitis, and patients with generalized periodontitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Periodontitis patients and controls were recruited, all aged \u2265\u200940\u2009years. Study participants were asked to rinse vigorously for 30\u2009s with 10\u2009mL phosphate buffered saline. Metabolites were identified using a semi\u2010targeted liquid chromatography tandem mass spectrometry (LC\u2013MS\/MS) platform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 38 periodontitis patients (18 localized, 20 generalized stage III\/IV periodontitis patients) and 16 controls were included. Metabolomic profiles of oral rinse samples were able to distinguish patients with severe periodontitis (stage III\/IV) from non\u2010periodontitis controls. Among various variables for the severity of periodontitis, we found that the number of sites with deep pockets (PPD) \u2265\u20096\u2009mm explained best the differences in metabolomic profiles between controls and patients with severe periodontitis. Subjects with a high number of sites with PPD \u2265\u20096\u2009mm were characterized by a higher level of phosphorylated nucleotides, amino acids, peptides, and dicarboxylic acids. Metabolomic profiles were also significantly different between controls vs. generalized periodontitis and between localized periodontitis vs. generalized periodontitis (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrates that simply collected oral rinse samples are suitable for LC\u2013MS\/MS based metabolomic analysis. We show that a metabolomic profile with a substantial number of metabolites can distinguish severe periodontitis patients from non\u2010periodontitis controls. These observations can be a basis for further studies into screening to identify subjects with the risk of having severe periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13379","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T03:49:34Z","timestamp":1741924174000},"page":"762-774","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolomic Profiles of Oral Rinse Samples to Distinguish Severe Periodontitis Patients From Non\u2010Periodontitis Controls"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6018-2753","authenticated-orcid":false,"given":"Madeline X. F.","family":"Kosho","sequence":"first","affiliation":[{"name":"Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8550-5379","authenticated-orcid":false,"given":"Alessio","family":"Ciurli","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology and Oncode Institute Leiden University Medical Center  Leiden the Netherlands"},{"name":"Leiden University Medical Center Center for Proteomics and Metabolomics  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1684-1894","authenticated-orcid":false,"given":"Martin","family":"Giera","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Center for Proteomics and Metabolomics  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-2211","authenticated-orcid":false,"given":"Jacques","family":"Neefjes","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology and Oncode Institute Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8794-552X","authenticated-orcid":false,"given":"Bruno G.","family":"Loos","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12297"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67728-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13769"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13337"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12436"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.202100384"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11090587"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-022-01940-5"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-020-01754-3"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-023-02040-8"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-021-00728-6"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00056"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-04612-x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11587"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102768"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.101002"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.108884"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.07.045120"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2012.110664"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.17-0721"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.1072215"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3393"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-007-0082-2"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/2047-217X-2-13"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2011.335"},{"key":"e_1_2_10_27_1","unstructured":"R.DerksandE.Nevedomskaya \u201cRcpm: Quality Control\u2010based Robust LOESS Signal Correction \u201dhttps:\/\/github.com\/RicoDerks\/Rcpm."},{"key":"e_1_2_10_28_1","unstructured":"R Core Team \u201cA Language and Environment for Statistical Computing. R Foundation for Statistical Computing \u201d2023Vienna Austria https:\/\/www.R\u2010project.org\/."},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01686"},{"key":"e_1_2_10_30_1","doi-asserted-by":"crossref","unstructured":"T. L.Pedersen \u201cggforce: Accelerating \u201cggplot2\u201d \u201d2016[cited 2024 Jul 9]. p. 0.4.2 https:\/\/CRAN.R\u2010project.org\/package=ggforce.","DOI":"10.32614\/CRAN.package.ggforce"},{"key":"e_1_2_10_31_1","doi-asserted-by":"crossref","unstructured":"H.Wickham T. L.Pedersen andD.Seidel \u201cscales: Scale Functions for Visualization \u201d2011[cited 2024 Jul 9]. p. 1.3.0 https:\/\/CRAN.R\u2010project.org\/package=scales.","DOI":"10.32614\/CRAN.package.scales"},{"key":"e_1_2_10_32_1","doi-asserted-by":"crossref","unstructured":"T. L.Pedersen \u201cpatchwork: The Composer of Plots \u201d2019[cited 2024 Jul 9]. p. 1.2.0 https:\/\/CRAN.R\u2010project.org\/package=patchwork.","DOI":"10.32614\/CRAN.package.patchwork"},{"key":"e_1_2_10_33_1","unstructured":"E.Th\u00e9venot \u201cRopls \u201d2017[cited 2024 Jul 9] https:\/\/bioconductor.org\/packages\/ropls."},{"key":"e_1_2_10_34_1","doi-asserted-by":"crossref","unstructured":"R.Kolde \u201cpheatmap: Pretty Heatmaps \u201d2010[cited 2024 Jul 9]. p. 1.0.12 https:\/\/CRAN.R\u2010project.org\/package=pheatmap.","DOI":"10.32614\/CRAN.package.pheatmap"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.706907"},{"key":"e_1_2_10_36_1","doi-asserted-by":"crossref","unstructured":"T.WeiandV.Simko \u201ccorrplot: Visualization of a Correlation Matrix \u201d2010[cited 2024 Jul 9]. p. 0.92 https:\/\/CRAN.R\u2010project.org\/package=corrplot.","DOI":"10.32614\/CRAN.package.corrplot"},{"key":"e_1_2_10_37_1","doi-asserted-by":"crossref","unstructured":"A.Kassambara \u201cggpubr: \u201cggplot2\u201d Based Publication Ready Plots \u201d2016[cited 2024 Jul 9]. p. 0.6.0 https:\/\/CRAN.R\u2010project.org\/package=ggpubr.","DOI":"10.32614\/CRAN.package.ggpubr"},{"key":"e_1_2_10_38_1","doi-asserted-by":"crossref","unstructured":"A.Kassambara \u201crstatix: Pipe\u2010Friendly Framework for Basic Statistical Tests \u201d2019[cited 2024 Jul 9]. p. 0.7.2 https:\/\/CRAN.R\u2010project.org\/package=rstatix.","DOI":"10.32614\/CRAN.package.rstatix"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034519842853"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.09.009"},{"issue":"05","key":"e_1_2_10_41_1","first-page":"S1","article-title":"Citicoline: Pharmacological and Clinical Review, 2022 Update","volume":"75","author":"Secades J. J.","year":"2022","journal-title":"Revista de Neurologia"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105181"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2015.04.004"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2020.104963"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-021-03977-7"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034511416240"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-009-0178-y"},{"issue":"8","key":"e_1_2_10_48_1","first-page":"3154","article-title":"Possible Prognostic Biomarkers of Periodontitis in Saliva","volume":"25","author":"Kluknavsk\u00e1 J.","year":"2021","journal-title":"European Review for Medical and Pharmacological Sciences"},{"issue":"2","key":"e_1_2_10_49_1","first-page":"63","article-title":"Determination of Oxidative Stress Parameters and Tissue Factor Activity in the Saliva of Patients With Periodontitis","volume":"78","author":"Oktay S.","year":"2019","journal-title":"European Journal of Biology"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:NERE.0000010440.37629.17"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-012-1361-4"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-595X.2002.tb00928.x"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169157"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40104-016-0139-z"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389203720666190305163135"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.4103\/1735-3327.166169"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2018.11.002"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-011-0331-2"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-017-1245-4"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2018.10.023"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13167-020-00202-5"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2023.11.001"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111389"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3NP00037K"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1081\/IPH-120029947"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1080\/1354750X.2021.1875506"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2008.00104.x"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2021.132403"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12872"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516661142"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13870"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-012799"}],"container-title":["Journal of Periodontal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jre.13379","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T06:55:46Z","timestamp":1760338546000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jre.13379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,14]]},"references-count":71,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/jre.13379"],"URL":"https:\/\/doi.org\/10.1111\/jre.13379","archive":["Portico"],"relation":{},"ISSN":["0022-3484","1600-0765"],"issn-type":[{"value":"0022-3484","type":"print"},{"value":"1600-0765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,14]]},"assertion":[{"value":"2024-09-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}