{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:57:56Z","timestamp":1793167076746,"version":"4.5.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the Key Project of Nature Science Research Project of Anhui Provincial Department of Education","award":["KJ2019A0266"],"award-info":[{"award-number":["KJ2019A0266"]}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"crossref","award":["ZR2017MH026"],"award-info":[{"award-number":["ZR2017MH026"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81771076"],"award-info":[{"award-number":["81771076"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81630072-2"],"award-info":[{"award-number":["81630072-2"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Construction Engineering Special Fund of \u201cTaishan Scholars\u201d"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We aimed to explore the effects of type-2 diabetes mellitus (T2DM) and hypoglycemic therapy on the salivary microbiome in periodontitis patients and identify the potential salivary micro-biomarker for the early warning of T2DM. Saliva samples were collected from healthy individuals (Health), periodontitis patients (P), T2DM patients, periodontitis patients with T2DM (DAP), and DAP patients treated with Metformin (Met). Samples were determined by16S rRNA gene sequencing. 29 phyla, 322 genera, and 333 species of salivary microbiome were annotated. Compared to the Health group, the P and DAP group showed a significantly higher diversity of saliva microbiota, while the T2DM and Met group had no significant difference in microbial abundance but showed a trend of increasing diversity. Other than well-known periodontitis-inducing pathogens, the proportion of <jats:italic>Prevotella copri<\/jats:italic>, <jats:italic>Alloprevotella rava<\/jats:italic>, and <jats:italic>Ralstonia pickettii<\/jats:italic>, etc. were also significantly increased in periodontitis patients with or without T2DM. After effective glycemic control, the abundance of <jats:italic>Prevotella copri<\/jats:italic>, <jats:italic>Alloprevotella rava<\/jats:italic>, <jats:italic>Ralstonia pickettii<\/jats:italic>, etc. decreased in periodontitis patients with companion T2DM. The accuracies of the classification models in differentiating Health-vs.-P, DAP-vs.-P, and T2DM-vs.-P were 100%, 96.3%, and 98.1%, respectively. Hypoglycemic therapy could reconstruct the saliva microbiota and hence improve the localized conditions of diabetes patients with periodontitis.<\/jats:p>","DOI":"10.1038\/s41598-020-72035-1","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T10:03:11Z","timestamp":1600682591000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Alteration of salivary microbiome in periodontitis with or without type-2 diabetes mellitus and metformin treatment"],"prefix":"10.1038","volume":"10","author":[{"given":"Xiaoyu","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenjun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jike","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pishan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,21]]},"reference":[{"key":"72035_CR1","first-page":"2","volume":"21","author":"X Wang","year":"2017","unstructured":"Wang, X. The 4th national oral disease epidemiology survey report. People\u2019s Med. Publ. House 21, 2 (2017).","journal-title":"People\u2019s Med. Publ. House"},{"key":"72035_CR2","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.ejim.2010.07.011","volume":"21","author":"G Pizzo","year":"2010","unstructured":"Pizzo, G. et al. Dentistry and internal medicine: from the focal infection theory to the periodontal medicine concept. Eur. J. Intern. Med. 21, 496\u2013502 (2010).","journal-title":"Eur. J. Intern. Med."},{"key":"72035_CR3","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1089\/dna.2009.0874","volume":"28","author":"M Avila","year":"2009","unstructured":"Avila, M., Ojcius, D. M. & Yilmaz, O. The oral microbiota: Living with a permanent guest. DNA Cell Biol. 28, 405\u2013411 (2009).","journal-title":"DNA Cell Biol."},{"issue":"42","key":"72035_CR4","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1111\/j.1600-0757.2006.00174.x","volume":"2000","author":"BJ Paster","year":"2006","unstructured":"Paster, B. J. et al. The breadth of bacterial diversity in the human periodontal pocket and other oral sites. Periodontol 2000(42), 80\u201387 (2006).","journal-title":"Periodontol"},{"key":"72035_CR5","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/S2213-8587(18)30136-0","volume":"7","author":"A Ceriello","year":"2019","unstructured":"Ceriello, A., Monnier, L. & Owens, D. Glycaemic variability in diabetes: Clinical and therapeutic implications. Lancet Diabetes Endocrinol. 7, 221\u2013230 (2019).","journal-title":"Lancet Diabetes Endocrinol."},{"key":"72035_CR6","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41415-019-0794-5","volume":"227","author":"PM Preshaw","year":"2019","unstructured":"Preshaw, P. M. & Bissett, S. M. Periodontitis and diabetes. Br. Dent. J. 227, 577\u2013584 (2019).","journal-title":"Br. Dent. J."},{"key":"72035_CR7","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1016\/j.dsx.2019.03.023","volume":"13","author":"AI Khumaedi","year":"2019","unstructured":"Khumaedi, A. I. et al. The relationship of diabetes, periodontitis and cardiovascular disease. Diabetes Metab. Syndr. 13, 1675\u20131678 (2019).","journal-title":"Diabetes Metab. Syndr."},{"key":"72035_CR8","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1038\/nrendo.2011.106","volume":"7","author":"E Lalla","year":"2011","unstructured":"Lalla, E. & Papapanou, P. N. Daibetes mellitus and periodontitis: a tale of two common interrelated diseases. Nat. Rev. Endocrinol. 7, 738\u2013748 (2011).","journal-title":"Nat. Rev. Endocrinol."},{"key":"72035_CR9","doi-asserted-by":"publisher","first-page":"e0183506","DOI":"10.1371\/journal.pone.0183506","volume":"12","author":"AA Ara\u00fajo","year":"2017","unstructured":"Ara\u00fajo, A. A. et al. Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis. PLoS ONE 12, e0183506 (2017).","journal-title":"PLoS ONE"},{"key":"72035_CR10","doi-asserted-by":"publisher","first-page":"e105181","DOI":"10.1371\/journal.pone.0105181","volume":"9","author":"VM Barnes","year":"2014","unstructured":"Barnes, V. M. et al. Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease. PLoS ONE 9, e105181 (2014).","journal-title":"PLoS ONE"},{"key":"72035_CR11","doi-asserted-by":"publisher","first-page":"421","DOI":"10.2337\/dc09-1378","volume":"33","author":"WJ Teeuw","year":"2010","unstructured":"Teeuw, W. J., Gerdes, V. E. & Loos, B. G. Effect of periodontal treatment on glycemic control of diabetic patients: A systematic review and meta-analysis. Diabetes Care 33, 421\u2013427 (2010).","journal-title":"Diabetes Care"},{"issue":"4 Suppl","key":"72035_CR12","doi-asserted-by":"crossref","first-page":"S113","DOI":"10.1111\/jcpe.12059","volume":"84","author":"JJ Taylor","year":"2013","unstructured":"Taylor, J. J., Preshaw, P. M. & Lalla, E. A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J. Periodontol 84(4 Suppl), S113\u2013S134 (2013).","journal-title":"J. Periodontol"},{"key":"72035_CR13","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s40496-016-0079-x","volume":"3","author":"KT Simpson","year":"2016","unstructured":"Simpson, K. T. & Thomas, J. G. Oral microbiome: Contributions to local and systemic infections. Curr. Oral Health Rep. 3, 45\u201355 (2016).","journal-title":"Curr. Oral Health Rep."},{"key":"72035_CR14","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1111\/j.1399-302X.2007.00426.x","volume":"23","author":"N Makiura","year":"2008","unstructured":"Makiura, N. et al. Relationship of Porphyromonas gingivalis with glycemic level in patients with type 2 diabetes following periodontal treatment. Oral Microbiol. Immunol. 23, 348\u2013351 (2008).","journal-title":"Oral Microbiol. Immunol."},{"key":"72035_CR15","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.anaerobe.2013.06.010","volume":"22","author":"P Aemaimanan","year":"2013","unstructured":"Aemaimanan, P., Amimanan, P. & Taweechaisupapong, S. Quantification of key periodontal pathogens in insulin-dependent type 2 diabetic and non-diabetic patients with generalized chronic periodontitis. Anaerobe 22, 64\u201368 (2013).","journal-title":"Anaerobe"},{"key":"72035_CR16","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1902\/jop.2008.070455","volume":"79","author":"JL Ebersole","year":"2008","unstructured":"Ebersole, J. L. et al. Microbiologic and immunologic characteristics of periodontal disease in Hispanic americans with type 2 diabetes. J. Periodontol 79, 637\u2013646 (2008).","journal-title":"J. Periodontol"},{"key":"72035_CR17","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.diabres.2017.06.009","volume":"130","author":"R Anbalagan","year":"2017","unstructured":"Anbalagan, R. et al. Next generation sequencing of oral microbiota in type 2 diabetes mellitus prior to and after neem stick usage and correlation with serum monocyte chemoattractant-1. Diabetes Res. Clin. Pract. 130, 204\u2013210 (2017).","journal-title":"Diabetes Res. Clin. Pract."},{"key":"72035_CR18","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1111\/jre.12432","volume":"52","author":"J Long","year":"2017","unstructured":"Long, J. et al. Association of oral microbiome with type 2 diabetes risk. J. Periodontal. Res. 52, 636\u2013643 (2017).","journal-title":"J. Periodontal. Res."},{"key":"72035_CR19","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1111\/j.1399-302X.2007.00341.x","volume":"22","author":"J Hintao","year":"2007","unstructured":"Hintao, J. et al. The microbiological profiles of saliva, supragingival and subgingival plaque and dental caries in adults with and without type 2 diabetes mellitus. Oral Microbiol. Immunol. 22, 175\u2013181 (2007).","journal-title":"Oral Microbiol. Immunol."},{"key":"72035_CR20","doi-asserted-by":"publisher","first-page":"201","DOI":"10.2334\/josnusd.16-0856","volume":"59","author":"Y Yamashita","year":"2017","unstructured":"Yamashita, Y. & Takeshita, T. The oral microbiome and human health. J. Oral Sci. 59, 201\u2013206 (2017).","journal-title":"J. Oral Sci."},{"key":"72035_CR21","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-318977","author":"J Wang","year":"2019","unstructured":"Wang, J. et al. Tracing the accumulation of in vivo human oral microbiome elucidates microbial community dynamics at the gateway to the GI tract. Gut https:\/\/doi.org\/10.1136\/gutjnl-2019-318977 (2019).","journal-title":"Gut"},{"key":"72035_CR22","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/JPER.18-0167","volume":"90","author":"A Sabharwal","year":"2019","unstructured":"Sabharwal, A. et al. The salivary microbiome of diabetic and non-diabetic adults with periodontal disease. J. Periodontol. 90, 26\u201334 (2019).","journal-title":"J. Periodontol."},{"key":"72035_CR23","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1136\/gutjnl-2015-309897","volume":"66","author":"V Blasco-Baque","year":"2017","unstructured":"Blasco-Baque, V. et al. Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response. Gut 66, 872\u2013885 (2017).","journal-title":"Gut"},{"key":"72035_CR24","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1111\/jcpe.12803","volume":"45","author":"D Polak","year":"2018","unstructured":"Polak, D. & Shapira, L. An update on the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J. Clin. Periodontol 45, 150\u2013166 (2018).","journal-title":"J. Clin. Periodontol"},{"key":"72035_CR25","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1080\/15321819.2018.1550423","volume":"40","author":"H Ahsan","year":"2019","unstructured":"Ahsan, H. Biomolecules and biomarkers in oral cavity: Bioassays and immunopathology. J. Immunoassay Immunochem. 40, 52\u201369 (2019).","journal-title":"J. Immunoassay Immunochem."},{"key":"72035_CR26","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/ijos.2016.38","volume":"8","author":"CZ Zhang","year":"2016","unstructured":"Zhang, C. Z. et al. Saliva in the diagnosis of diseases. Int. J. Oral Sci. 8, 133\u2013137 (2016).","journal-title":"Int. J. Oral Sci."},{"issue":"Suppl 1","key":"72035_CR27","doi-asserted-by":"publisher","first-page":"S73","DOI":"10.2337\/dc18-S008","volume":"41","author":"American Diabetes Association","year":"2018","unstructured":"American Diabetes Association. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes-2018. Diabetes Care 41(Suppl 1), S73\u2013S85 (2018).","journal-title":"Diabetes Care"},{"key":"72035_CR28","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/nm.4345","volume":"23","author":"H Wu","year":"2017","unstructured":"Wu, H. et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23, 850\u2013858 (2017).","journal-title":"Nat. Med."},{"key":"72035_CR29","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.micpath.2019.01.009","volume":"128","author":"ATM Saeb","year":"2019","unstructured":"Saeb, A. T. M. et al. Relative reduction of biological and phylogenetic diversity of the oral microbiota of diabetes and pre-diabetes patients. Microb. Pathog. 128, 215\u2013229 (2019).","journal-title":"Microb. Pathog."},{"key":"72035_CR30","first-page":"151","volume":"6","author":"ZZ Li","year":"2017","unstructured":"Li, Z. Z. et al. Aanlysis of oral microbial diversity in patients with type 2 diabetes mellitus by 16Sribosome DNA amplicon sequencing. Transl. Med. J. 6, 151\u2013156 (2017).","journal-title":"Transl. Med. J."},{"key":"72035_CR31","doi-asserted-by":"publisher","first-page":"6990","DOI":"10.1038\/srep06990","volume":"4","author":"T Takeshita","year":"2014","unstructured":"Takeshita, T. et al. Distinct composition of the oral indigenous microbiota in South Korea and Japanese adults. Sci. Rep. 4, 6990 (2014).","journal-title":"Sci. Rep."},{"key":"72035_CR32","doi-asserted-by":"publisher","first-page":"e23352","DOI":"10.1371\/journal.pone.0023352","volume":"6","author":"I Nasidze","year":"2011","unstructured":"Nasidze, I. et al. High diversity of the saliva microbiome in Batwa Pygmies. PLoS ONE 6, e23352 (2011).","journal-title":"PLoS ONE"},{"key":"72035_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1902\/annals.1999.4.1.1","volume":"4","author":"GC Armitage","year":"1999","unstructured":"Armitage, G. C. Development of a classification system for periodontal diseases and conditions. Ann. Periodontol 4, 1\u20136 (1999).","journal-title":"Ann. Periodontol"},{"key":"72035_CR34","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1007\/s00125-018-4729-5","volume":"61","author":"MJ Davies","year":"2018","unstructured":"Davies, M. J. et al. Management of hyperglycaemia in type 2 diabetes, 2018 A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 61, 2461\u20132498 (2018).","journal-title":"Diabetologia"},{"key":"72035_CR35","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1902\/jop.2012.110664","volume":"83","author":"PI Eke","year":"2012","unstructured":"Eke, P. I. et al. Update of the case definitions for population-based surveillance of periodontitis. J. Periodontol. 83, 1449\u20131454 (2012).","journal-title":"J. Periodontol."},{"key":"72035_CR36","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1177\/00220345920710060201","volume":"71","author":"M Navazesh","year":"1992","unstructured":"Navazesh, M. et al. Comparison of whole saliva flow rates and mucin concentrations in healthy Caucasian young and aged adults. J. Dent. Res. 71, 1275\u20131278 (1992).","journal-title":"J. Dent. Res."},{"key":"72035_CR37","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/database\/baq013","volume":"2010","author":"T Chen","year":"2010","unstructured":"Chen, T. et al. The Human Oral Microbiome Database: A web accessible resource for investigating oral microbe taxonomic and genomic information. Database (Oxford) 2010, 13 (2010).","journal-title":"Database (Oxford)"},{"key":"72035_CR38","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1002\/j.1538-7305.1948.tb00917.x","volume":"27","author":"CE Shannon","year":"1948","unstructured":"Shannon, C. E. A mathematical theory of communication. Bell. Syst. Tech. J. 27, 623\u2013656 (1948).","journal-title":"Bell. Syst. Tech. J."},{"key":"72035_CR39","first-page":"265","volume":"11","author":"A Chao","year":"1984","unstructured":"Chao, A. Non-parametric estimation of the classes in a population. Scand. J. Stat. 11, 265\u2013270 (1984).","journal-title":"Scand. J. Stat."},{"key":"72035_CR40","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","volume":"37","author":"E Bolyen","year":"2019","unstructured":"Bolyen, E. et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotech. 37, 852\u2013857 (2019).","journal-title":"Nat. Biotech."},{"key":"72035_CR41","unstructured":"Oksanen, J., et al. Package Vegan: Community Ecology package, version 2.0 10. (2013) https:\/\/cran.r-project.org."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72035-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72035-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72035-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T19:28:28Z","timestamp":1670354908000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72035-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,21]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["72035"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-72035-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,21]]},"assertion":[{"value":"4 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15363"}}