Current Oral Health Reports

, Volume 4, Issue 2, pp 158–166 | Cite as

Periodontal Medicine—New Diagnostic Opportunities

  • Ricardo TelesEmail author
Systemic Diseases (M Bartold, section editor)
Part of the following topical collections:
  1. Topical Collection on Systemic Diseases


Purpose of Review

We examined the literature on periodontal medicine to determine how this field has influenced the diagnosis of periodontal diseases and the search for biomarkers in oral fluids.

Recent Findings

Periodontal medicine has pushed the boundaries of biomarker discovery in oral fluids, where several analytes present in serum can be detected and potentially explored for the diagnosis of systemic conditions. The study of mechanisms linking oral and systemic diseases has also contributed to advances in our understanding of systemic modulation of the subgingival microenvironment and its effects on gingival crevicular fluid components and the local microbiota.


Recent technological advances in “omics” platforms allow us to examine concomitantly functional changes that occur in the host and the resident microbiota during disease processes. Integration of multi-omics data such as the one proposed by the Integrative Human Microbiome Project will afford new insights into the interplay between oral and systemic diseases.


Periodontal diseases Systemic adverse outcomes Biomarkers Saliva Gingival crevicular fluid Microbiome 


Compliance with Ethical Standards

Conflict of Interest

The author declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Offenbacher S. Periodontal diseases: pathogenesis. Ann Periodontol. 1996;1(1):821–78.CrossRefPubMedGoogle Scholar
  2. 2.
    Van Dyke TE, van Winkelhoff AJ. Infection and inflammatory mechanisms. J Clin Periodontol. 2013;40(Suppl 14):S1–7. doi: 10.1111/jcpe.12088.PubMedGoogle Scholar
  3. 3.
    Southerland JH, Taylor GW, Moss K, Beck JD, Offenbacher S. Commonality in chronic inflammatory diseases: periodontitis, diabetes, and coronary artery disease. Periodontol. 2006;40:130–43. doi: 10.1111/j.1600-0757.2005.00138.x.CrossRefGoogle Scholar
  4. 4.
    Giannobile WV, McDevitt JT, Niedbala RS, Malamud D. Translational and clinical applications of salivary diagnostics. Adv Dent Res. 23(4):375–80. doi: 10.1177/0022034511420434.
  5. 5.
    Wong DT. Salivaomics. J Am Dent Assoc. 2012;143(10 Suppl):19s–24s.CrossRefPubMedGoogle Scholar
  6. 6.
    Hefti AF. Periodontal probing. Crit Rev Oral Biol Med. 1997;8(3):336–56.CrossRefPubMedGoogle Scholar
  7. 7.
    Haffajee AD, Socransky SS, Goodson JM. Clinical parameters as predictors of destructive periodontal disease activity. J Clin Periodontol. 1983;10(3):257–65.CrossRefPubMedGoogle Scholar
  8. 8.
    Grossi SG, Dunford RG, Ho A, Koch G, Machtei EE, Genco RJ. Sources of error for periodontal probing measurements. J Periodontal Res. 1996;31(5):330–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Espeland MA, Zappa UE, Hogan PE, Simona C, Graf H. Cross-sectional and longitudinal reliability for clinical measurement of attachment loss. J Clin Periodontol. 1991;18(2):126–33.CrossRefPubMedGoogle Scholar
  10. 10.
    Beck JD, Offenbacher S. Relationships among clinical measures of periodontal disease and their associations with systemic markers. Ann Periodontol. 2002;7(1):79–89. doi: 10.1902/annals.2002.7.1.79.CrossRefPubMedGoogle Scholar
  11. 11.
    Ide M, Papapanou PN. Epidemiology of association between maternal periodontal disease and adverse pregnancy outcomes—systematic review. J Periodontol. 2013;84(4 Suppl):S181–94. doi: 10.1902/jop.2013.134009.PubMedGoogle Scholar
  12. 12.
    Linden GJ, Lyons A, Scannapieco FA. Periodontal systemic associations: review of the evidence. J Clin Periodontol. 2013;40(Suppl 14):S8–19. doi: 10.1111/jcpe.12064.PubMedGoogle Scholar
  13. 13.
    Hujoel PP, White BA, Garcia RI, Listgarten MA. The dentogingival epithelial surface area revisited. J Periodontal Res. 2001;36(1):48–55.CrossRefPubMedGoogle Scholar
  14. 14.
    Schwahn C, Volzke H, Robinson DM, Luedemann J, Bernhardt O, Gesch D, et al. Periodontal disease, but not edentulism, is independently associated with increased plasma fibrinogen levels. Results from a population-based study. Thromb Haemost. 2004;92(2):244–52. doi: 10.1160/TH04-02-0092.PubMedGoogle Scholar
  15. 15.
    Dietrich T, Jimenez M, Krall Kaye EA, Vokonas PS, Garcia RI. Age-dependent associations between chronic periodontitis/edentulism and risk of coronary heart disease. Circulation. 2008;117(13):1668–74. doi: 10.1161/CIRCULATIONAHA.107.711507.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Nesse W, Abbas F, van der Ploeg I, Spijkervet FK, Dijkstra PU, Vissink A. Periodontal inflamed surface area: quantifying inflammatory burden. J Clin Periodontol. 2008;35(8):668–73. doi: 10.1111/j.1600-051X.2008.01249.x.CrossRefPubMedGoogle Scholar
  17. 17.
    Offenbacher S, Barros SP, Singer RE, Moss K, Williams RC, Beck JD. Periodontal disease at the biofilm-gingival interface. J Periodontol. 2007;78(10):1911–25. doi: 10.1902/jop.2007.060465.CrossRefPubMedGoogle Scholar
  18. 18.
    Ebersole JL, Cappelli D. Acute-phase reactants in infections and inflammatory diseases. Periodontol. 2000;23:19–49.CrossRefGoogle Scholar
  19. 19.
    Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868–74. doi: 10.1038/nature01323.CrossRefPubMedGoogle Scholar
  20. 20.
    Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon 3rd RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107(3):499–511.CrossRefPubMedGoogle Scholar
  21. 21.
    Paraskevas S, Huizinga JD, Loos BG. A systematic review and meta-analyses on C-reactive protein in relation to periodontitis. J Clin Periodontol. 2008;35(4):277–90. doi: 10.1111/j.1600-051X.2007.01173.x.CrossRefPubMedGoogle Scholar
  22. 22.
    Yoshii S, Tsuboi S, Morita I, Takami Y, Adachi K, Inukai J, et al. Temporal association of elevated C-reactive protein and periodontal disease in men. J Periodontol. 2009;80(5):734–9. doi: 10.1902/jop.2009.080537.CrossRefPubMedGoogle Scholar
  23. 23.
    Loos BG. Systemic markers of inflammation in periodontitis. J Periodontol. 2005;76(11 Suppl):2106–15. doi: 10.1902/jop.2005.76.11-S.2106.CrossRefPubMedGoogle Scholar
  24. 24.
    Buhlin K, Hultin M, Norderyd O, Persson L, Pockley AG, Rabe P, et al. Risk factors for atherosclerosis in cases with severe periodontitis. J Clin Periodontol. 2009;36(7):541–9. doi: 10.1111/j.1600-051X.2009.01430.x.CrossRefPubMedGoogle Scholar
  25. 25.
    D'Aiuto F, Orlandi M, Gunsolley JC. Evidence that periodontal treatment improves biomarkers and CVD outcomes. J Clin Periodontol. 2013;40(Suppl 14):S85–105. doi: 10.1111/jcpe.12061.CrossRefPubMedGoogle Scholar
  26. 26.
    Ioannidou E, Malekzadeh T, Dongari-Bagtzoglou A. Effect of periodontal treatment on serum C-reactive protein levels: a systematic review and meta-analysis. J Periodontol. 2006;77(10):1635–42. doi: 10.1902/jop.2006.050443.CrossRefPubMedGoogle Scholar
  27. 27.
    Freitas CO, Gomes-Filho IS, Naves RC, Nogueira Filho Gda R, Cruz SS, Santos CA, et al. Influence of periodontal therapy on C-reactive protein level: a systematic review and meta-analysis. J Appl Oral Sci. 2012;20(1):1–8.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Teles R, Wang CY. Mechanisms involved in the association between periodontal diseases and cardiovascular disease. Oral Dis. 2011;17(5):450–61. doi: 10.1111/j.1601-0825.2010.01784.x.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Teles RP, Likhari V, Socransky SS, Haffajee AD. Salivary cytokine levels in subjects with chronic periodontitis and in periodontally healthy individuals: a cross-sectional study. J Periodontal Res. 2009;44(3):411–7. doi: 10.1111/j.1600-0765.2008.01119.x.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Yoshizawa JM, Schafer CA, Schafer JJ, Farrell JJ, Paster BJ, Wong DT. Salivary biomarkers: toward future clinical and diagnostic utilities. Clin Microbiol Rev. 2013;26(4):781–91. doi: 10.1128/cmr.00021-13.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Zhang Y, Sun J, Lin CC, Abemayor E, Wang MB, Wong DT. The emerging landscape of salivary diagnostics. Periodontol. 2016;70(1):38–52. doi: 10.1111/prd.12099.CrossRefGoogle Scholar
  32. 32.
    Browne RW, Kantarci A, LaMonte MJ, Andrews CA, Hovey KM, Falkner KL, et al. Performance of multiplex cytokine assays in serum and saliva among community-dwelling postmenopausal women. PLoS One. 2013;8(4):e59498. doi: 10.1371/journal.pone.0059498.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ebersole JL, Kryscio RJ, Campbell C, Kinane DF, McDevitt J, Christodoulides N, et al. Salivary and serum adiponectin and C-reactive protein levels in acute myocardial infarction related to body mass index and oral health. J Periodontal Res. 2016; doi: 10.1111/jre.12406.Google Scholar
  34. 34.
    Redman RS, Kerr GS, Payne JB, Mikuls TR, Huang J, Sayles HR, et al. Salivary and serum procalcitonin and C-reactive protein as biomarkers of periodontitis in United States veterans with osteoarthritis or rheumatoid arthritis. Biotech Histochem. 2016;91(2):77–85. doi: 10.3109/10520295.2015.1082625.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Gumus P, Emingil G, Ozturk VO, Belibasakis GN, Bostanci N. Oxidative stress markers in saliva and periodontal disease status: modulation during pregnancy and postpartum. BMC Infect Dis. 2015;15:261. doi: 10.1186/s12879-015-1003-z.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Lamster IB, Ahlo JK. Analysis of gingival crevicular fluid as applied to the diagnosis of oral and systemic diseases. Ann N Y Acad Sci. 2007;1098:216–29. doi: 10.1196/annals.1384.027.CrossRefPubMedGoogle Scholar
  37. 37.
    Wassall RR, Preshaw PM. Clinical and technical considerations in the analysis of gingival crevicular fluid. Periodontol. 2016;70(1):65–79. doi: 10.1111/prd.12109.CrossRefGoogle Scholar
  38. 38.
    Back M, Airila-Mansson S, Jogestrand T, Soder B, Soder PO. Increased leukotriene concentrations in gingival crevicular fluid from subjects with periodontal disease and atherosclerosis. Atherosclerosis. 2007;193(2):389–94. doi: 10.1016/j.atherosclerosis.2006.07.003.CrossRefPubMedGoogle Scholar
  39. 39.
    Shah R, Thomas R, Mehta DS. Oxidized-low density lipoprotein in gingival crevicular fluid of patients with chronic periodontitis: a possible link to atherogenesis. Acta Odontol Scand. 2014;72(2):154–6. doi: 10.3109/00016357.2013.810772.CrossRefPubMedGoogle Scholar
  40. 40.
    Chen H, Zheng P, Zhu H, Zhu J, Zhao L, El Mokhtari NE, et al. Platelet-activating factor levels of serum and gingival crevicular fluid in nonsmoking patients with periodontitis and/or coronary heart disease. Clin Oral Investig. 2010;14(6):629–36. doi: 10.1007/s00784-009-0346-5.CrossRefPubMedGoogle Scholar
  41. 41.
    Hayashi S, Yamada H, Fukui M, Ito HO, Sata M. Correlation between arteriosclerosis and periodontal condition assessed by lactoferrin and alpha1-antitrypsin levels in gingival crevicular fluid. Int Heart J. 2015;56(6):639–43. doi: 10.1536/ihj.15-218.CrossRefPubMedGoogle Scholar
  42. 42.
    Wytrykowska A, Prosba-Mackiewicz M, Nyka WM. IL-1beta, TNF-alpha, and IL-6 levels in gingival fluid and serum of patients with ischemic stroke. J Oral Sci. 2016;58(4):509–13. doi: 10.2334/josnusd.16-0278.CrossRefPubMedGoogle Scholar
  43. 43.
    Tuter G, Kurtis B, Serdar M. Evaluation of gingival crevicular fluid and serum levels of high-sensitivity C-reactive protein in chronic periodontitis patients with or without coronary artery disease. J Periodontol. 2007;78(12):2319–24. doi: 10.1902/jop.2007.070150.CrossRefPubMedGoogle Scholar
  44. 44.
    Fitzsimmons TR, Sanders AE, Bartold PM, Slade GD. Local and systemic biomarkers in gingival crevicular fluid increase odds of periodontitis. J Clin Periodontol. 2010;37(1):30–6. doi: 10.1111/j.1600-051X.2009.01506.x.CrossRefPubMedGoogle Scholar
  45. 45.
    Megson E, Fitzsimmons T, Dharmapatni K, Bartold PM. C-reactive protein in gingival crevicular fluid may be indicative of systemic inflammation. J Clin Periodontol. 2010;37(9):797–804. doi: 10.1111/j.1600-051X.2010.01603.x.CrossRefPubMedGoogle Scholar
  46. 46.
    Sorsa T, Mantyla P, Ronka H, Kallio P, Kallis GB, Lundqvist C, et al. Scientific basis of a matrix metalloproteinase-8 specific chair-side test for monitoring periodontal and peri-implant health and disease. Ann N Y Acad Sci. 1999;878:130–40.CrossRefPubMedGoogle Scholar
  47. 47.
    Mantyla P, Stenman M, Kinane DF, Tikanoja S, Luoto H, Salo T, et al. Gingival crevicular fluid collagenase-2 (MMP-8) test stick for chair-side monitoring of periodontitis. J Periodontal Res. 2003;38(4):436–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Uitto VJ, Overall CM, McCulloch C. Proteolytic host cell enzymes in gingival crevice fluid. Periodontol. 2003;31:77–104.CrossRefGoogle Scholar
  49. 49.
    Herman MP, Sukhova GK, Libby P, Gerdes N, Tang N, Horton DB, et al. Expression of neutrophil collagenase (matrix metalloproteinase-8) in human atheroma: a novel collagenolytic pathway suggested by transcriptional profiling. Circulation. 2001;104(16):1899–904.CrossRefPubMedGoogle Scholar
  50. 50.
    Blankenberg S, Rupprecht HJ, Poirier O, Bickel C, Smieja M, Hafner G, et al. Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation. 2003;107(12):1579–85. doi: 10.1161/01.CIR.0000058700.41738.12.CrossRefPubMedGoogle Scholar
  51. 51.
    Tuomainen AM, Nyyssonen K, Laukkanen JA, Tervahartiala T, Tuomainen TP, Salonen JT, et al. Serum matrix metalloproteinase-8 concentrations are associated with cardiovascular outcome in men. Arterioscler Thromb Vasc Biol. 2007;27(12):2722–8. doi: 10.1161/ATVBAHA.107.154831.CrossRefPubMedGoogle Scholar
  52. 52.
    Brown DL, Desai KK, Vakili BA, Nouneh C, Lee HM, Golub LM. Clinical and biochemical results of the metalloproteinase inhibition with subantimicrobial doses of doxycycline to prevent acute coronary syndromes (MIDAS) pilot trial. Arterioscler Thromb Vasc Biol. 2004;24(4):733–8. doi: 10.1161/01.ATV.0000121571.78696.dc.CrossRefPubMedGoogle Scholar
  53. 53.
    • Bench TJ, Jeremias A, Brown DL. Matrix metalloproteinase inhibition with tetracyclines for the treatment of coronary artery disease. Pharmacol Res. 2011;64(6):561–6. doi: 10.1016/j.phrs.2011.05.002. This paper reviews how our current understanding of the role of MMPs in the pathogenesis of atherosclerosis led to the testing of the effects of low-dose doxycycline, a drug that has been used to control periodontal disease progression, on patients with coronary artery disease. The authors summarize the results of the Metalloproteinase Inhibition with subantimicrobial dose Doxycycline to prevent Acute coronary Syndromes (MIDAS) trial, which demonstrated a 46% reduction in CRP levels, and a 54% reduction in MMP-9 activity. Of interest, the 46% reduction in CRP levels occurred in patients who were already taking statins, which also reduces CRP. CrossRefPubMedGoogle Scholar
  54. 54.
    Tuter G, Kurtis B, Serdar M, Aykan T, Okyay K, Yucel A, et al. Effects of scaling and root planing and sub-antimicrobial dose doxycycline on oral and systemic biomarkers of disease in patients with both chronic periodontitis and coronary artery disease. J Clin Periodontol. 2007;34(8):673–81. doi: 10.1111/j.1600-051X.2007.01104.x.CrossRefPubMedGoogle Scholar
  55. 55.
    Golub LM, Lee HM, Stoner JA, Sorsa T, Reinhardt RA, Wolff MS, et al. Subantimicrobial-dose doxycycline modulates gingival crevicular fluid biomarkers of periodontitis in postmenopausal osteopenic women. J Periodontol. 2008;79(8):1409–18. doi: 10.1902/jop.2008.070623.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Payne JB, Golub LM, Stoner JA, Lee HM, Reinhardt RA, Sorsa T, et al. The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial. J Am Dent Assoc. 2011;142(3):262–73.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Han YW, Wang X. Mobile microbiome: oral bacteria in extra-oral infections and inflammation. J Dent Res. 2013;92(6):485–91. doi: 10.1177/0022034513487559.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Cairo F, Gaeta C, Dorigo W, Oggioni MR, Pratesi C, Pini Prato GP, et al. Periodontal pathogens in atheromatous plaques. A controlled clinical and laboratory trial. J Periodontal Res. 2004;39(6):442–6. doi: 10.1111/j.1600-0765.2004.00761.x.CrossRefPubMedGoogle Scholar
  59. 59.
    Ford PJ, Gemmell E, Chan A, Carter CL, Walker PJ, Bird PS, et al. Inflammation, heat shock proteins and periodontal pathogens in atherosclerosis: an immunohistologic study. Oral Microbiol Immunol. 2006;21(4):206–11. doi: 10.1111/j.1399-302X.2006.00276.x.CrossRefPubMedGoogle Scholar
  60. 60.
    Wang X, Buhimschi CS, Temoin S, Bhandari V, Han YW, Buhimschi IA. Comparative microbial analysis of paired amniotic fluid and cord blood from pregnancies complicated by preterm birth and early-onset neonatal sepsis. PLoS One. 2013;8(2):e56131. doi: 10.1371/journal.pone.0056131.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Martinez-Martinez RE, Abud-Mendoza C, Patino-Marin N, Rizo-Rodriguez JC, Little JW, Loyola-Rodriguez JP. Detection of periodontal bacterial DNA in serum and synovial fluid in refractory rheumatoid arthritis patients. J Clin Periodontol. 2009;36(12):1004–10. doi: 10.1111/j.1600-051X.2009.01496.x.CrossRefPubMedGoogle Scholar
  62. 62.
    Heo SM, Sung RS, Scannapieco FA, Haase EM. Genetic relationships between Candida albicans strains isolated from dental plaque, trachea, and bronchoalveolar lavage fluid from mechanically ventilated intensive care unit patients. J Oral Microbiol. 2011;3 doi: 10.3402/jom.v3i0.6362.
  63. 63.
    Shinzato T, Saito A. The Streptococcus milleri group as a cause of pulmonary infections. Clin Infect Dis. 1995;21(Suppl 3):S238–43.CrossRefPubMedGoogle Scholar
  64. 64.
    Miklossy J. Emerging roles of pathogens in Alzheimer disease. Expert Rev Mol Med. 2011;13:e30. doi: 10.1017/S1462399411002006.CrossRefPubMedGoogle Scholar
  65. 65.
    Kumar PS. From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease. J Physiol. 2017;595(2):465–76. doi: 10.1113/JP272427.CrossRefPubMedGoogle Scholar
  66. 66.
    • Zhou M, Rong R, Munro D, Zhu C, Gao X, Zhang Q, et al. Investigation of the effect of type 2 diabetes mellitus on subgingival plaque microbiota by high-throughput 16S rDNA pyrosequencing. PLoS One. 2013;8(4):e61516. doi: 10.1371/journal.pone.0061516. Using next-generation sequencing, the authors characterized the composition of the subgingival microbiota in four groups of subjects separated based on the diagnoses of diabetes and periodontitis. The study revealed that the ecological changes in the subgingival environment that accompany hyperglycemia were followed by an increase in the levels of certain species such as P. gingivalis , T. medium , T. forsythia , P. endodontalis , F. alocis , and Leptotrichia spp. in periodontitis subjects. This is a novel finding because up until recently, the composition of the subgingival microbiota had not been demonstrated to be affected by diabetes. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Taylor JJ, Preshaw PM, Lalla E. A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J Clin Periodontol. 2013;40(Suppl 14):S113–34. doi: 10.1111/jcpe.12059.PubMedGoogle Scholar
  68. 68.
    •• Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra65. doi: 10.1126/scitranslmed.3008599. In this study, the microbiome of the placenta was examined for the first time using metagenomics techniques. The results revealed that the placenta seems be contaminated by microorganisms from the oral microbiota such as P. tannerae . Further, the placental microbiome was associated with preterm birth <37 weeks. The use of metagenomics also allowed the investigators to estimate which high-level metabolic pathways were part of the microbiome detected in the placental samples, giving some insights into its functional potential. CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Duran-Pinedo AE, Chen T, Teles R, Starr JR, Wang X, Krishnan K, et al. Community-wide transcriptome of the oral microbiome in subjects with and without periodontitis. ISME J. 2014;8(8):1659–72. doi: 10.1038/ismej.2014.23.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Yost S, Duran-Pinedo AE, Teles R, Krishnan K, Frias-Lopez J. Functional signatures of oral dysbiosis during periodontitis progression revealed by microbial metatranscriptome analysis. Genome Med. 2015;7(1):27. doi: 10.1186/s13073-015-0153-3.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Human Microbiome Project C. A framework for human microbiome research. Nature. 2012;486(7402):215–21. doi: 10.1038/nature11209.CrossRefGoogle Scholar
  72. 72.
    Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14. doi: 10.1038/nature11234.CrossRefGoogle Scholar
  73. 73.
    •• Integrative HMPRNC. The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe. 2014;16(3):276–89. doi: 10.1016/j.chom.2014.08.014. This article describes in details the projects being developed under the iHMP, which is the second phase of the HMP initiative from NIH. The paper describes the three models of microbiome-associated human conditions that will be studied in this second phase, including pregnancy and preterm birth, inflammatory bowel disease, and type 2 diabetes. Further, the multi-omic data types to be collected, integrated, and distributed through public repositories as a community resource are also described in details. The goal is to examine host-microbe interactions by analyzing microbiome and host activities in longitudinal studies. This unparalleled amount of information on how the microbiome interacts with the human host at different body sites in health and disease will allow the testing of a multitude of hypotheses about these interactions. In particular, the study on pregnancy will also obtain oral samples, providing an invaluable opportunity to examine the oral systemic link. CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of PeriodontologyUNC School of DentistryChapel HillUSA
  2. 2.Department of Applied Oral SciencesForsyth InstituteCambridgeUSA

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