Oral Biology pp 127-138 | Cite as

The Oral Microbiota in Health and Disease: An Overview of Molecular Findings

  • José F. SiqueiraJr.Email author
  • Isabela N. Rôças
Part of the Methods in Molecular Biology book series (MIMB, volume 1537)


Culture-independent nucleic acid technologies have been extensively applied to the analysis of oral bacterial communities associated with healthy and diseased conditions. These methods have confirmed and substantially expanded the findings from culture studies to reveal the oral microbial inhabitants and candidate pathogens associated with the major oral diseases. Over 1000 bacterial distinct species-level taxa have been identified in the oral cavity and studies using next-generation DNA sequencing approaches indicate that the breadth of bacterial diversity may be even much larger. Nucleic acid technologies have also been helpful in profiling bacterial communities and identifying disease-related patterns. This chapter provides an overview of the diversity and taxonomy of oral bacteria associated with health and disease.

Key words

Oral microbiology Molecular biology methods Taxonomy Oral diseases 


  1. 1.
    Ursell LK, Metcalf JL, Parfrey LW, Knight R (2012) Defining the human microbiome. Nutr Rev 70(Suppl 1):S38–S44CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI (2007) The human microbiome project. Nature 449:804–810CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Wade WG (2013) Characterisation of the human oral microbiome. J Oral Biosci 55:143–148CrossRefGoogle Scholar
  4. 4.
    Leys EJ, Griffen AL, Kumar PS, Maiden MF (2006) Isolation, classification, and identification of oral microorganisms. In: Lamont RJ, Burne RA, Lantz MS, Leblanc DJ (eds) Oral microbiology and immunology. ASM Press, Washington, DC, pp 73–88Google Scholar
  5. 5.
    Siqueira JF Jr, Rôças IN (2013) As-yet-uncultivated oral bacteria: breadth and association with oral and extra-oral diseases. J Oral Microbiol 5:doi:  10.3402/jom.v3405i3400.21077
  6. 6.
    Sizova MV, Hohmann T, Hazen A, Paster BJ, Halem SR, Murphy CM, Panikov NS, Epstein SS (2012) New approaches for isolation of previously uncultivated oral bacteria. Appl Environ Microbiol 78:194–203CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Socransky SS, Gibbons RJ, Dale AC, Bortnick L, Rosenthal E, MacDonald JB (1963) The microbiota of the gingival crevice in man. 1. Total microscopic and viable counts and counts of specific organisms. Arch Oral Biol 8:275–280CrossRefPubMedGoogle Scholar
  8. 8.
    Voelkerding KV, Dames SA, Durtschi JD (2009) Next-generation sequencing: from basic research to diagnostics. Clin Chem 55:641–658CrossRefPubMedGoogle Scholar
  9. 9.
    Paster BJ, Olsen I, Aas JA, Dewhirst FE (2006) The breadth of bacterial diversity in the human periodontal pocket and other oral sites. Periodontol 2000 42:80–87CrossRefPubMedGoogle Scholar
  10. 10.
    Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, Lakshmanan A, Wade WG (2010) The human oral microbiome. J Bacteriol 192:5002–5017CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE (2005) Defining the normal bacterial flora of the oral cavity. J Clin Microbiol 43:5721–5732CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kazor CE, Mitchell PM, Lee AM, Stokes LN, Loesche WJ, Dewhirst FE, Paster BJ (2003) Diversity of bacterial populations on the tongue dorsa of patients with halitosis and healthy patients. J Clin Microbiol 41:558–563CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Paster BJ, Falkler Jr WA Jr, Enwonwu CO, Idigbe EO, Savage KO, Levanos VA, Tamer MA, Ericson RL, Lau CN, Dewhirst FE (2002) Prevalent bacterial species and novel phylotypes in advanced noma lesions. J Clin Microbiol 40:2187–2191CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Paster BJ, Boches SK, Galvin JL, Ericson RE, Lau CN, Levanos VA, Sahasrabudhe A, Dewhirst FE (2001) Bacterial diversity in human subgingival plaque. J Bacteriol 183:3770–3783CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    de Lillo A, Ashley FP, Palmer RM, Munson MA, Kyriacou L, Weightman AJ, Wade WG (2006) Novel subgingival bacterial phylotypes detected using multiple universal polymerase chain reaction primer sets. Oral Microbiol Immunol 21:61–68CrossRefPubMedGoogle Scholar
  16. 16.
    Aas JA, Barbuto SM, Alpagot T, Olsen I, Dewhirst FE, Paster BJ (2007) Subgingival plaque microbiota in HIV positive patients. J Clin Periodontol 34:189–195CrossRefPubMedGoogle Scholar
  17. 17.
    Huyghe A, Francois P, Charbonnier Y, Tangomo-Bento M, Bonetti EJ, Paster BJ, Bolivar I, Baratti-Mayer D, Pittet D, Schrenzel J, Geneva Study Group on Noma (GESNOMA) (2008) Novel microarray design strategy to study complex bacterial communities. Appl Environ Microbiol 74:1876–1885CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Keijser BJ, Zaura E, Huse SM, van der Vossen JM, Schuren FH, Montijn RC, ten Cate JM, Crielaard W (2008) Pyrosequencing analysis of the oral microflora of healthy adults. J Dent Res 87:1016–1020CrossRefPubMedGoogle Scholar
  19. 19.
    Zaura E, Keijser BJ, Huse SM, Crielaard W (2009) Defining the healthy “core microbiome” of oral microbial communities. BMC Microbiol 9:259CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Crielaard W, Zaura E, Schuller AA, Huse SM, Montijn RC, Keijser BJ (2011) Exploring the oral microbiota of children at various developmental stages of their dentition in the relation to their oral health. BMC Med Genomics 4:22CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lazarevic V, Whiteson K, Hernandez D, Francois P, Schrenzel J (2010) Study of inter- and intra-individual variations in the salivary microbiota. BMC Genomics 11:523CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Zhou M, Rong R, Munro D, Zhu C, Gao X, Zhang Q, Dong Q (2013) Investigation of the effect of type 2 diabetes mellitus on subgingival plaque microbiota by high-throughput 16S rDNA pyrosequencing. PLoS One 8, e61516CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Ferreira DC, Gonçalves LS, Siqueira JF Jr, Carmo FL, Santos HF, Feres M, Figueiredo LC, Soares GM, Rosado AS, dos Santos KR, Colombo AP (2015) Subgingival bacterial community profiles in HIV-infected Brazilian adults with chronic periodontitis. J Periodontal Res 51:95–102CrossRefPubMedGoogle Scholar
  24. 24.
    Ghannoum MA, Jurevic RJ, Mukherjee PK, Cui F, Sikaroodi M, Naqvi A, Gillevet PM (2010) Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog 6:e1000713CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Marsh P, Martin MV (1999) Oral microbiology, 4th edn. Wright, OxfordGoogle Scholar
  26. 26.
    Bowden GH (2000) The microbial ecology of dental caries. Microb Ecol Health Dis 12:138–148CrossRefGoogle Scholar
  27. 27.
    Belda-Ferre P, Alcaraz LD, Cabrera-Rubio R, Romero H, Simón-Soro A, Pignatelli M, Mira A (2012) The oral metagenome in health and disease. ISME J 6:46–56CrossRefPubMedGoogle Scholar
  28. 28.
    Schulze-Schweifing K, Banerjee A, Wade WG (2014) Comparison of bacterial culture and 16S rRNA community profiling by clonal analysis and pyrosequencing for the characterization of the dentine caries-associated microbiome. Front Cell Infect Microbiol 4:164CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Jiang W, Ling Z, Lin X, Chen Y, Zhang J, Yu J, Xiang C, Chen H (2014) Pyrosequencing analysis of oral microbiota shifting in various caries states in childhood. Microb Ecol 67:962–969CrossRefPubMedGoogle Scholar
  30. 30.
    Prez D, Olsen I, Aas JA, Willumsen T, Grinde B, Paster BJ (2008) Bacterial profiles of root caries in elderly patients. J Clin Microbiol 46:2015–2021CrossRefGoogle Scholar
  31. 31.
    Aas JA, Dardis SR, Griffen AL, Stokes LN, Lee AM, Olsen I, Dewhirst FE, Leys EJ, Paster BJ (2003) Molecular analysis of bacteria associated with caries in permanent teeth. J Dent Res 82 (Spec Iss A):IADR Abstract No. 1025.
  32. 32.
    Munson MA, Banerjee A, Watson TF, Wade WG (2004) Molecular analysis of the microflora associated with dental caries. J Clin Microbiol 42:3023–3029CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Aas JA, Dardis SR, Griffen AL, Stokes LN, Lee AM, Olsen I, Dewhirs FE, Leys EJ, Paster BJ (2005) Most of the microbiota in caries has not yet been cultivated. J Dent Res 84 (Spec Iss A), IADR Abstract No 2805.
  34. 34.
    Aas JA, Griffen AL, Dardis SR, Lee AM, Olsen I, Dewhirst FE, Leys EJ, Paster BJ (2008) Bacteria of dental caries in primary and permanent teeth in children and young adults. J Clin Microbiol 46:1407–1417CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Becker MR, Paster BJ, Leys EJ, Moeschberger ML, Kenyon SG, Galvin JL, Boches SK, Dewhirst FE, Griffen AL (2002) Molecular analysis of bacterial species associated with childhood caries. J Clin Microbiol 40:1001–1009CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Lima KC, Coelho LT, Pinheiro IV, Rôças IN, Siqueira JF Jr (2011) Microbiota of dentinal caries as assessed by reverse-capture checkerboard analysis. Caries Res 45:21–30CrossRefPubMedGoogle Scholar
  37. 37.
    Kianoush N, Adler CJ, Nguyen KA, Browne GV, Simonian M, Hunter N (2014) Bacterial profile of dentine caries and the impact of pH on bacterial population diversity. PLoS One 9, e92940CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Nadkarni MA, Caldon CE, Chhour KL, Fisher IP, Martin FE, Jacques NA, Hunter N (2004) Carious dentine provides a habitat for a complex array of novel Prevotella-like bacteria. J Clin Microbiol 42:5238–5244CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Martin FE, Nadkarni MA, Jacques NA, Hunter N (2002) Quantitative microbiological study of human carious dentine by culture and real-time PCR: association of anaerobes with histopathological changes in chronic pulpitis. J Clin Microbiol 40:1698–1704CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Chhour KL, Nadkarni MA, Byun R, Martin FE, Jacques NA, Hunter N (2005) Molecular analysis of microbial diversity in advanced caries. J Clin Microbiol 43:843–849CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ling Z, Kong J, Jia P, Wei C, Wang Y, Pan Z, Huang W, Li L, Chen H, Xiang C (2010) Analysis of oral microbiota in children with dental caries by PCR-DGGE and barcoded pyrosequencing. Microb Ecol 60:677–690CrossRefPubMedGoogle Scholar
  42. 42.
    Rôças IN, Lima KC, Assuncao IV, Gomes PN, Bracks IV, Siqueira JF Jr (2015) Advanced caries microbiota in teeth with irreversible pulpitis. J Endod 41:1450–1455CrossRefPubMedGoogle Scholar
  43. 43.
    Chen L, Qin B, Du M, Zhong H, Xu Q, Li Y, Zhang P, Fan M (2015) Extensive description and comparison of human supra-gingival microbiome in root caries and health. PLoS One 10, e0117064CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Jiang W, Zhang J, Chen H (2013) Pyrosequencing analysis of oral microbiota in children with severe early childhood dental caries. Curr Microbiol 67:537–542CrossRefPubMedGoogle Scholar
  45. 45.
    Loesche WJ, Kazor C (2002) Microbiology and treatment of halitosis. Periodontol 2000 28:256–279CrossRefPubMedGoogle Scholar
  46. 46.
    Lamont RJ, Hajishengallis G (2015) Polymicrobial synergy and dysbiosis in inflammatory disease. Trends Mol Med 21:172–183CrossRefPubMedGoogle Scholar
  47. 47.
    Hajishengallis G, Lamont RJ (2014) Breaking bad: manipulation of the host response by Porphyromonas gingivalis. Eur J Immunol 44:328–338CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr (1998) Microbial complexes in subgingival plaque. J Clin Periodontol 25:134–144CrossRefPubMedGoogle Scholar
  49. 49.
    Sakamoto M, Huang Y, Umeda M, Ishikawa I, Benno Y (2002) Detection of novel oral phylotypes associated with periodontitis. FEMS Microbiol Lett 217:65–69CrossRefPubMedGoogle Scholar
  50. 50.
    Griffen AL, Kumar PS, Leys EJ (2003) A quantitative, molecular view of oral biofilm communities in health and disease suggests a role for uncultivated species, polymicrobial diseases. American Society for Microbiology Conferences, Lake Tahoe, Nevada, p 13Google Scholar
  51. 51.
    Kumar PS, Griffen AL, Barton JA, Paster BJ, Moeschberger ML, Leys EJ (2003) New bacterial species associated with chronic periodontitis. J Dent Res 82:338–344CrossRefPubMedGoogle Scholar
  52. 52.
    Kumar PS, Griffen AL, Moeschberger ML, Leys EJ (2005) Identification of candidate periodontal pathogens and beneficial species by quantitative 16S clonal analysis. J Clin Microbiol 43:3944–3955CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Brinig MM, Lepp PW, Ouverney CC, Armitage GC, Relman DA (2003) Prevalence of bacteria of division TM7 in human subgingival plaque and their association with disease. Appl Environ Microbiol 69:1687–1694CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Harper-Owen R, Dymock D, Booth V, Weightman AJ, Wade WG (1999) Detection of unculturable bacteria in periodontal health and disease by PCR. J Clin Microbiol 37:1469–1473PubMedPubMedCentralGoogle Scholar
  55. 55.
    Park OJ, Yi H, Jeon JH, Kang SS, Koo KT, Kum KY, Chun J, Yun CH, Han SH (2015) Pyrosequencing analysis of subgingival microbiota in distinct periodontal conditions. J Dent Res 94:921–927CrossRefPubMedGoogle Scholar
  56. 56.
    Griffen AL, Beall CJ, Campbell JH, Firestone ND, Kumar PS, Yang ZK, Podar M, Leys EJ (2012) Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyrosequencing. ISME J 6:1176–1185CrossRefPubMedGoogle Scholar
  57. 57.
    Abusleme L, Dupuy AK, Dutzan N, Silva N, Burleson JA, Strausbaugh LD, Gamonal J, Diaz PI (2013) The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. ISME J 7:1016–1025CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Camelo-Castillo AJ, Mira A, Pico A, Nibali L, Henderson B, Donos N, Tomas I (2015) Subgingival microbiota in health compared to periodontitis and the influence of smoking. Front Microbiol 6:119CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Moon JH, Lee JH, Lee JY (2015) Subgingival microbiome in smokers and non-smokers in Korean chronic periodontitis patients. Mol Oral Microbiol 30:227–241CrossRefPubMedGoogle Scholar
  60. 60.
    Lepp PW, Brinig MM, Ouverney CC, Palm K, Armitage GC, Relman DA (2004) Methanogenic Archaea and human periodontal disease. Proc Natl Acad Sci U S A 101:6176–6181CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Slots J (2005) Herpesviruses in periodontal diseases. Periodontol 2000 38:33–62CrossRefPubMedGoogle Scholar
  62. 62.
    Slots J (2010) Human viruses in periodontitis. Periodontol 2000 53:89–110CrossRefPubMedGoogle Scholar
  63. 63.
    Siqueira JF Jr (2002) Endodontic infections: concepts, paradigms, and perspectives. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 94:281–293CrossRefPubMedGoogle Scholar
  64. 64.
    Siqueira JF Jr, Rôças IN (2009) Diversity of endodontic microbiota revisited. J Dent Res 88:969–981CrossRefPubMedGoogle Scholar
  65. 65.
    Sundqvist G, Figdor D, Persson S, Sjogren U (1998) Microbiologic analysis of teeth with failed endodontic treatment and the outcome of conservative re-treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:86–93CrossRefPubMedGoogle Scholar
  66. 66.
    Rôças IN, Siqueira JF Jr (2012) Characterization of microbiota of root canal-treated teeth with posttreatment disease. J Clin Microbiol 50:1721–1724CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Li L, Hsiao WW, Nandakumar R, Barbuto SM, Mongodin EF, Paster BJ, Fraser-Liggett CM, Fouad AF (2010) Analyzing endodontic infections by deep coverage pyrosequencing. J Dent Res 89:980–984CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Siqueira JF Jr, Alves FR, Rôças IN (2011) Pyrosequencing analysis of the apical root canal microbiota. J Endod 37:1499–1503CrossRefPubMedGoogle Scholar
  69. 69.
    Ozok AR, Persoon IF, Huse SM, Keijser BJ, Wesselink PR, Crielaard W, Zaura E (2012) Ecology of the microbiome of the infected root canal system: a comparison between apical and coronal root segments. Int Endod J 45:530–541CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Santos AL, Siqueira JF Jr, Rôças IN, Jesus EC, Rosado AS, Tiedje JM (2011) Comparing the bacterial diversity of acute and chronic dental root canal infections. PLoS One 6, e28088CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Hong BY, Lee TK, Lim SM, Chang SW, Park J, Han SH, Zhu Q, Safavi KE, Fouad AF, Kum KY (2013) Microbial analysis in primary and persistent endodontic infections by using pyrosequencing. J Endod 39:1136–1140CrossRefPubMedGoogle Scholar
  72. 72.
    Vengerfeldt V, Špilka K, Saag M, Preem JK, Oopkaup K, Truu J, Mändar R (2014) Highly diverse microbiota in dental root canals in cases of apical periodontitis (data of illumina sequencing). J Endod 40:1778–1783CrossRefPubMedGoogle Scholar
  73. 73.
    Anderson AC, Al-Ahmad A, Elamin F, Jonas D, Mirghani Y, Schilhabel M, Karygianni L, Hellwig E, Rehman A (2013) Comparison of the bacterial composition and structure in symptomatic and asymptomatic endodontic infections associated with root-filled teeth using pyrosequencing. PLoS One 8, e84960CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Tzanetakis GN, Azcarate-Peril MA, Zachaki S, Panopoulos P, Kontakiotis EG, Madianos PN, Divaris K (2015) Comparison of bacterial community composition of primary and persistent endodontic infections using pyrosequencing. J Endod 41:1226–1233CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Department ofEndodontics, Molecular Microbiology LaboratoryEstácio de Sá UniversityRio de JaneiroBrazil
  2. 2.Faculty of DentistryEstácio de Sá UniversityRio de JaneiroBrazil

Personalised recommendations