Current Oral Health Reports

, Volume 6, Issue 2, pp 138–144 | Cite as

Computational Analysis of Interactions of the Oral Microbiota

  • Ryan S. McClureEmail author
Microbiology (C Genco, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Microbiology


Purpose of Review

The human oral microbiome is a complex site containing many hundreds of species with the community response of these species having a large effect on human health. The complexity of this site speaks to the need for applying -omics techniques to better understand which microbial species are present, their interactions and contribution to the microbiome, and how this may change as a function of disease. Here, I review several recent studies that use computational analysis to examine and model the oral microbiome and determine its role in human health.

Recent Findings

Several studies have emerged in the past few years that use several -omics approaches to look specifically at points of interaction between microbiomes of the oral cavity and between these microbiomes and the human host. New techniques in sequencing have revealed a more detailed picture of who is present and their interactions. Network studies that attempt to link hundreds of species, transcripts, or proteins are also beginning to be inferred though their use, aside from species co-abundance networks, are still in the early stages.


The ability to collect -omics data of the oral microbiome has been well established. The future of this field will likely focus on the integration and use of this data to build models that reveal hundreds of interactions between species at the individual gene or protein level. A better understanding of these interactions, and how they contribute to disease states, will allow for better control and manipulation of the oral microbiome to improve human health.


Oral cavity Microbiome -omics Interspecies interactions Computational Modeling 


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.
    Escapa IF, Chen T, Huang Y, Gajare P, Dewhirst FE, Lemon KP. New insights into human nostril microbiome from the expanded human oral microbiome database (eHOMD): a resource for the microbiome of the human aerodigestive tract. mSystems. 2018;3(6).Google Scholar
  2. 2.
    Jia G, Zhi A, Lai PFH, Wang G, Xia Y, Xiong Z, et al. The oral microbiota - a mechanistic role for systemic diseases. Br Dent J. 2018;224(6):447–55.CrossRefPubMedGoogle Scholar
  3. 3.
    Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner ACR, Yu WH, et al. The human oral microbiome. J Bacteriol. 2010;192(19):5002–17.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Zaura E, Keijser BJF, Huse SM, Crielaard W. Defining the healthy “core microbiome” of oral microbial communities. BMC Microbiol. 2009;9:259.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Gibson FC 3rd, Genco CA. Porphyromonas gingivalis mediated periodontal disease and atherosclerosis: disparate diseases with commonalities in pathogenesis through TLRs. Curr Pharm Des. 2007;13(36):3665–75.CrossRefPubMedGoogle Scholar
  6. 6.
    Hayashi C, Viereck J, Hua N, Phinikaridou A, Madrigal AG, Gibson FC III, et al. Porphyromonas gingivalis accelerates inflammatory atherosclerosis in the innominate artery of ApoE deficient mice. Atherosclerosis. 2011;215(1):52–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Kim HJ, Cha GS, Kim HJ, Kwon EY, Lee JY, Choi J, et al. Porphyromonas gingivalis accelerates atherosclerosis through oxidation of high-density lipoprotein. J Periodontal Implant Sci. 2018;48(1):60–8.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    • Ebbers M, Lübcke PM, Volzke J, Kriebel K, Hieke C, Engelmann R, et al. Interplay between P. gingivalis, F. nucleatum, and A. actinomycetemcomitans in murine alveolar bone loss, arthritis onset and progression. Sci Rep. 2018;8(1):15129 This paper describes specific interspecies interactions centered on pathogens that related to oral health. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Lin M, et al. Different engagement of TLR2 and TLR4 in Porphyromonas gingivalis vs. ligature-induced periodontal bone loss. Braz Oral Res. 2017;31:e63.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Nises J, Rosander A, Pettersson A, Backhans A. The occurrence of Treponema spp. in gingival plaque from dogs with varying degree of periodontal disease. PLoS One. 2018;13(8):e0201888.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Sochocka M, Zwolinska K, Leszek J. The infectious etiology of Alzheimer’s disease. Curr Neuropharmacol. 2017;15(7):996–1009.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Siqueira JF Jr, Rocas IN. Community as the unit of pathogenicity: an emerging concept as to the microbial pathogenesis of apical periodontitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(6):870–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Yang L, Lu X, Nossa CW, Francois F, Peek RM, Pei Z. Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome. Gastroenterology. 2009;137(2):588–97.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kanasi E, Dewhirst FE, Chalmers NI, Kent R Jr, Moore A, Hughes CV, et al. Clonal analysis of the microbiota of severe early childhood caries. Caries Res. 2010;44(5):485–97.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Paster BJ, et al. The breadth of bacterial diversity in the human periodontal pocket and other oral sites. Periodontol 2000. 2006;42:80–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Kolenbrander PE, Palmer RJ, Periasamy S, Jakubovics NS. Oral multispecies biofilm development and the key role of cell-cell distance. Nat Rev Microbiol. 2010;8(7):471–80.CrossRefPubMedGoogle Scholar
  17. 17.
    Kuboniwa M, Tribble GD, James CE, Kilic AO, Tao L, Herzberg MC, et al. Streptococcus gordonii utilizes several distinct gene functions to recruit Porphyromonas gingivalis into a mixed community. Mol Microbiol. 2006;60(1):121–39.CrossRefPubMedGoogle Scholar
  18. 18.
    Kolenbrander PE, Andersen RN, Moore LV. Coaggregation of Fusobacterium nucleatum, Selenomonas flueggei, Selenomonas infelix, Selenomonas noxia, and Selenomonas sputigena with strains from 11 genera of oral bacteria. Infect Immun. 1989;57(10):3194–203.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Egland PG, Palmer RJ Jr, Kolenbrander PE. Interspecies communication in Streptococcus gordonii-Veillonella atypica biofilms: signaling in flow conditions requires juxtaposition. Proc Natl Acad Sci U S A. 2004;101(48):16917–22.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Simionato MR, Tucker CM, Kuboniwa M, Lamont G, Demuth DR, Tribble GD, et al. Porphyromonas gingivalis genes involved in community development with Streptococcus gordonii. Infect Immun. 2006;74(11):6419–28.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    •• Jasberg H, et al. Bifidobacteria inhibit the growth of Porphyromonas gingivalis but not of Streptococcus mutans in an in vitro biofilm model. Eur J Oral Sci. 2016;124(3):251–8 This paper described aspects of interactions that could be harnessed to improve oral health. CrossRefPubMedGoogle Scholar
  22. 22.
    •• Kobayashi R, et al. Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas gingivalis-accelerated periodontal disease. Sci Rep. 2017;7(1):545 This paper describes the same but moves toward exploring a practical application. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Jakubovics NS, Gill SR, Iobst SE, Vickerman MM, Kolenbrander PE. Regulation of gene expression in a mixed-genus community: stabilized arginine biosynthesis in Streptococcus gordonii by coaggregation with Actinomyces naeslundii. J Bacteriol. 2008;190(10):3646–57.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Bamford CV, d'Mello A, Nobbs AH, Dutton LC, Vickerman MM, Jenkinson HF. Streptococcus gordonii modulates Candida albicans biofilm formation through intergeneric communication. Infect Immun. 2009;77(9):3696–704.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Benn A, Heng NCK, Broadbent JM, Thomson WM. Studying the human oral microbiome: challenges and the evolution of solutions. Aust Dent J. 2018;63(1):14–24.CrossRefPubMedGoogle Scholar
  26. 26.
    Hugo P, Potworowski EF. Dynamics of complex formation between thymocytes and thymic medullary epithelial cells. Scand J Immunol. 1989;29(4):399–408.CrossRefPubMedGoogle Scholar
  27. 27.
    Verma D, Garg PK, Dubey AK. Insights into the human oral microbiome. Arch Microbiol. 2018;200(4):525–40.CrossRefPubMedGoogle Scholar
  28. 28.
    • Eren AM, Borisy GG, Huse SM, Mark Welch JL. Oligotyping analysis of the human oral microbiome. Proc Natl Acad Sci U S A. 2014;111(28):E2875–84 This paper applied a more stringent type of amplicon analysis to the oral cavity to better describe which specie are present. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Mukherjee C, Beall CJ, Griffen AL, Leys EJ. High-resolution ISR amplicon sequencing reveals personalized oral microbiome. Microbiome. 2018;6(1):153.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Jorth P, Turner KH, Gumus P, Nizam N, Buduneli N, Whiteley M. Metatranscriptomics of the human oral microbiome during health and disease. MBio. 2014;5(2):e01012–4.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Benitez-Paez A, et al. Microbiota diversity and gene expression dynamics in human oral biofilms. BMC Genomics. 2014;15:311.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Belstrom D, et al. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls. PeerJ. 2016;4:e2433.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Belda-Ferre P, Williamson J, Simón-Soro Á, Artacho A, Jensen ON, Mira A. The human oral metaproteome reveals potential biomarkers for caries disease. Proteomics. 2015;15(20):3497–507.CrossRefPubMedGoogle Scholar
  35. 35.
    Grassl N, Kulak NA, Pichler G, Geyer PE, Jung J, Schubert S, et al. Ultra-deep and quantitative saliva proteome reveals dynamics of the oral microbiome. Genome Med. 2016;8(1):44.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Kuboniwa M, Hendrickson EL, Xia Q, Wang T, Xie H, Hackett M, et al. Proteomics of Porphyromonas gingivalis within a model oral microbial community. BMC Microbiol. 2009;9:98.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    •• SCoelho ED, et al. Computational prediction of the human-microbial oral interactome. BMC Syst Biol. 2014;8:24 This paper used proteomics to predict interactions between the human host and the microbiome. CrossRefGoogle Scholar
  38. 38.
    Duran-Pinedo AE, Paster B, Teles R, Frias-Lopez J. Correlation network analysis applied to complex biofilm communities. PLoS One. 2011;6(12):e28438.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ghannoum MA, Jurevic RJ, Mukherjee PK, Cui F, Sikaroodi M, Naqvi A, et al. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog. 2010;6(1):e1000713.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Dupuy AK, David MS, Li L, Heider TN, Peterson JD, Montano EA, et al. Redefining the human oral mycobiome with improved practices in amplicon-based taxonomy: discovery of Malassezia as a prominent commensal. PLoS One. 2014;9(3):e90899.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    • Mukherjee PK, Chandra J, Retuerto M, Sikaroodi M, Brown RE, Jurevic R, et al. Oral mycobiome analysis of HIV-infected patients: identification of Pichia as an antagonist of opportunistic fungi. PLoS Pathog. 2014;10(3):e1003996 This paper describes the role of fungi in the oral microbiome and its relationship to oral health. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Shiba T, Watanabe T, Kachi H, Koyanagi T, Maruyama N, Murase K, et al. Distinct interacting core taxa in co-occurrence networks enable discrimination of polymicrobial oral diseases with similar symptoms. Sci Rep. 2016;6:30997.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Mark Welch JL, et al. Dynamics of tongue microbial communities with single-nucleotide resolution using oligotyping. Front Microbiol. 2014;5:568.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Wang J, Gao Y, Zhao F. Phage-bacteria interaction network in human oral microbiome. Environ Microbiol. 2016;18(7):2143–58.CrossRefPubMedGoogle Scholar
  45. 45.
    McClure RS, Overall CC, Hill EA, Song HS, Charania M, Bernstein HC, et al. Species-specific transcriptomic network inference of interspecies interactions. ISME J. 2018;12(8):2011–23.CrossRefPubMedGoogle Scholar
  46. 46.
    • Musungu BM, et al. A network approach of gene co-expression in the Zea mays/Aspergillus flavus Pathosystem to map host/pathogen interaction pathways. Front Genet. 2016;7:206 This paper was one of the first to infer a multi-species network focused on host-pathogen interactions. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Tierney L, et al. An interspecies regulatory network inferred from simultaneous RNA-seq of Candida albicans invading innate immune cells. Front Microbiol. 2012;3:85.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Faith JJ, Hayete B, Thaden JT, Mogno I, Wierzbowski J, Cottarel G, et al. Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles. PLoS Biol. 2007;5(1):e8.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Meyer PE, Lafitte F, Bontempi G. minet: A R/Bioconductor package for inferring large transcriptional networks using mutual information. BMC Bioinformatics. 2008;9:461.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Huynh-Thu VA, Irrthum A, Wehenkel L, Geurts P. Inferring regulatory networks from expression data using tree-based methods. PLoS One. 2010;5(9):e12776.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Haury AC, Mordelet F, Vera-Licona P, Vert JP. TIGRESS: trustful inference of gene regulation using stability selection. BMC Syst Biol. 2012;6:145.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Biological Sciences DivisionPacific Northwest National LaboratoryRichlandUSA
  2. 2.Microbiome Science Research GroupPacific Northwest National LaboratoryRichlandUSA

Personalised recommendations