Skip to main content

Advertisement

SpringerLink
Log in

Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis

  • Original Article
  • Published:
Odontology Aims and scope Submit manuscript

Abstract

There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous plaques from atherosclerosis patients with or without periodontitis to investigate the role of oral bacteria in the formation of atheromatous plaques. We chose four patients with and without periodontitis, who had undergone carotid endarterectomy. Bacterial samples were extracted from the tongue surface, from periodontal pocket (during the oral examination), and from the atheromatous plaques (APs). We investigated the general and oral conditions from each patient and performed next-generation sequencing (NGS) analysis for all bacterial samples. There were no significant differences between both groups concerning general conditions. However, the microbiome patterns of the gingival pocket showed differences depending on the absence or presence of periodontitis, while those of the tongue surface were relatively similar. The microbiome pattern of the atheromatous plaques was entirely different from that on the tongue surface and gingival pocket, and oral bacteria were seldom detected. However, the microbiome pattern in atheromatous plaques was different in the presence or absence of periodontitis. These results suggested that oral bacteria did not affect the formation of atheromatous plaques directly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

NGS:

Next-generation sequencing

LDL:

Low-density lipoprotein

Pg :

Porphyromonas gingivalis

Aa :

Aggregatibacter actinomycetemcomitans

Co :

Capnocytophaga ochracea

rRNA:

Ribosomal RNA

PPD:

Pocket probing depth

BOP:

Rate of bleeding on probing

PCA:

Principal component analysis

References

  1. Maddi A, Scannapieco FA. Oral biofilms, oral and periodontal infections, and systemic disease. Am J Dent. 2013;226:249–54 (PubMed PMID: 24479275).

    Google Scholar 

  2. Lalla E, Papapanou PN. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases. Nat Rev Endocrinol. 2011;7:738–48. https://doi.org/10.1038/nrendo.2011.106.

    Article  PubMed  Google Scholar 

  3. Senba T, Kobayashi Y, Inoue K, Kaneto C, Inoue M, Toyokawa S, et al. The association between self-reported periodontitis and coronary heart disease—from MY Health Up Study. J Occup Health. 2008;50:283–7.

    Article  PubMed  Google Scholar 

  4. Lafon A, Pereira B, Dufour T, Rigouby V, Giroud M, Béjot Y, et al. Periodontal disease and stroke: a meta-analysis of cohort studies. Eur J Neurol. 2014;21:1155–61, e66-7. https://doi.org/10.1111/ene.12415.

    Article  PubMed  Google Scholar 

  5. Isoshima D, Yamashiro K, Matsunaga K, Shinobe M, Nakanishi N, Nakanishi I, et al. Assessment of pathogenesis of infective endocarditis by plasma IgG antibody titer test against periodontal bacteria. Clin Case Rep. 2017;5:1580–6. https://doi.org/10.1002/ccr3.1066.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5:eaaau3333. https://doi.org/10.1126/sciadv.aau3333(eCollection 2019 Jan).

    Article  Google Scholar 

  7. Zeng XT, Deng AP, Li C, Xia LY, Niu YM, Leng WD. Periodontal disease and risk of head and neck cancer: a meta-analysis of observational studies. PLoS ONE. 2013;8:e79017. https://doi.org/10.1371/journal.pone.0079017.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Yoneda M, Naka S, Nakano K, Wada K, Endo H, Mawatari H, et al. Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease. BMC Gastroenterol. 2012;12:16. https://doi.org/10.1186/1471-230X-12-16(PubMed PMID: 22340817; PubMed Central).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Sanz M, Kornman K, Working group 3 of the joint EFP/AAP workshop. Periodontitis and adverse pregnancy outcomes: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Periodontol. 2013;84:S164–S169169. https://doi.org/10.1902/jop.2013.1340016.

    Article  PubMed  Google Scholar 

  10. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–26. https://doi.org/10.1056/NEJM199901143400207.

    Article  PubMed  Google Scholar 

  11. Vinchi F, Muckenthaler MU, Da Silva MC, Balla G, Balla J, Jeney V. Atherogenesis and iron: from epidemiology to cellular level. Front Pharmacol. 2014;5:94. https://doi.org/10.3389/fphar.2014.00094(eCollection 2014. Review).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bahekar AA, Singh S, Saha S, Molnar J, Arora R. The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: a meta-analysis. Am Heart J. 2007;154:830–7. https://doi.org/10.1016/j.ahj.2007.06.037.

    Article  PubMed  Google Scholar 

  13. Ishihara K, Nabuchi A, Ito R, Miyachi K, Kuramitsu HK, Okuda K. Correlation between detection rates of periodontopathic bacterial DNA in coronary stenotic artery plaque and in dental plaque samples. J Clin Microbiol. 2004;42:1313–5.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Okuda K, Ishihara K, Nakagawa T, Hirayama A, Inayama Y. Detection of treponema denticola in atherosclerotic lesions. J Clin Microbiol. 2001;39:1114–7. https://doi.org/10.1128/JCM.39.3.1114-1117.2001.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lockhart PB, Bolger AF, Papapanou PN, Osinbowale O, Trevisan M, Levison ME, et al. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association. Circulation. 2012;125:2520–44. https://doi.org/10.1161/CIR.0b013e31825719f3.

    Article  PubMed  Google Scholar 

  16. Hujoel PP, Drangsholt M, Spiekerman C, DeRouen TA. Periodontal disease and coronary heart disease risk. JAMA. 2000;284:1406–10.

    Article  PubMed  Google Scholar 

  17. Peacock ME, Carson RE. Frequency of self-reported medical conditions in periodontal patients. J Periodontol. 1999;66:1004–7. https://doi.org/10.1902/jop.1995.66.11.1004.

    Article  Google Scholar 

  18. Kurihara N, Inoue Y, Iwai T, Umeda M, Huang Y, Ishikawa I. Detection and localization of periodontopathic bacteria in abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2004;28:553–8. https://doi.org/10.1016/j.ejvs.2004.08.010.

    Article  PubMed  Google Scholar 

  19. Beck JD, Garcia RJ, Heiss G, Vokonas PS, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol. 1996;67:1123–37.

    Article  PubMed  Google Scholar 

  20. Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification of periodontal pathogens in atheromatous plaques. J Periodontol. 2000;71:1554–600.

    Article  PubMed  Google Scholar 

  21. Nakano K, Inaba H, Nomura R, Nemoto H, Takeuchi H, Yoshioka H, Toda K, Taniguchi K, Amano A, Ooshima T. Distribution of Porphyromonas gingivalis fimA genotypes in cardiovascular specimens from Japanese patients. Oral Microbiol Immunol. 2008;23:170–2.

    Article  PubMed  Google Scholar 

  22. Zaremba M, Górska R, Suwalski P, Kowalski J. Evaluation of the incidence of periodontitis-associated bacteria in the atherosclerotic plaque of coronary blood vessels. J Periodontol. 2007;78:322–7.

    Article  PubMed  Google Scholar 

  23. Szulc M, Kustrzycki W, Janczak D, Michalowska D, Baczynska D, Radwan-Oczko M. Presence of periodontopathic bacteria DNA in atheromatous plaques from coronary and carotid arteries. Biomed Res Int. 2015;2015:825397. https://doi.org/10.1155/2015/825397.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Serra e silva Filho W, Casarin RC, Nicolela EL Jr, Passos HM, Sallum AW, Gonçalves RB. Microbial diversity similarities in periodontal pockets and atheromatous plaques of cardiovascular disease patients. PLoS ONE. 2014;9:e109761. https://doi.org/10.1371/journal.pone.0109761.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kudo C, Shin WS, Minabe M, et al. Periodontitis and Atherosclerosis Project-Tokyo and Chiba Consortiums. Analysis of the relationship between periodontal disease and atherosclerosis within a local clinical system: a cross-sectional observational pilot study. Odontology. 2015;103:314–21. https://doi.org/10.1007/s10266-014-0172-3.

    Article  PubMed  Google Scholar 

  26. Li L, Messas E, Batista EL, Levine RA, Amar S. Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model. Circulation. 2002;105:861–7.

    Article  PubMed  Google Scholar 

  27. Ford PJ, Gemmell E, Timms P, Chan A, Preston FM, Seymour GJ. Anti-P. gingivalis response correlates with atherosclerosis. J Dent Res. 2007;86:35–40.

    Article  PubMed  Google Scholar 

  28. Maekawa T, Takahashi N, Tabeta K, Aoki Y, Miyashita H, Miyauchi S, Miyazawa H, Nakajima T, Yamazaki K. Chronic oral infection with Porphyromonas gingivalis accelerates atheroma formation by shifting the lipid profile. PLoS ONE. 2011;6:e20240.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Papapanou PN, Sellén A, Wennstr JL, Dahlén G. An analysis of the subgingival microflora in randomly selected subjects. Oral Microbiol Immunol. 1993;8:24–9.

    Article  PubMed  Google Scholar 

  30. Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, et al. Human genetics shape the gut microbiome. Cell. 2014;159:789–99. https://doi.org/10.1016/j.cell.2014.09.053.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature. 2015;517:205–8. https://doi.org/10.1038/nature13828.

    Article  PubMed  Google Scholar 

  32. Kudo C, Naruishi K, Maeda H, Abiko Y, Hino T, Iwata M, et al. Assessment of the plasma/serum IgG test to screen for periodontitis. J Dent Res. 2012;91:1190–5. https://doi.org/10.1177/0022034512461796.

    Article  PubMed  Google Scholar 

  33. Caton JG, Armitage G, Berglundh T, Chapple ILC, Jepsen S, Kornman KS, et al. A new classification scheme for periodontal and peri-implant diseases and conditions—introduction and key changes from the 1999 classification. J Periodontol. 2018;89(Suppl 1):S1–S8. https://doi.org/10.1002/JPER.18-0157.

    Article  PubMed  Google Scholar 

  34. Emery DC, Shoemark DK, Batstone TE, Waterfall CM, Coghill JA, Cerajewska TL, Davies M, West NX, Allen SJ. 16S rRNA next generation sequencing analysis shows bacteria in Alzheimer's post-mortem brain. Front Aging Neurosci. 2017. https://doi.org/10.3389/fnagi.2017.00195(eCollection 2017).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ziganshina EE, Sharifullina DM, Lozhkin AP, Khayrullin RN, Ignatyev IM, Ziganshin AM. Bacterial communities associated with atherosclerotic plaques from Russian individuals with atherosclerosis. PLoS ONE. 2016;11:e0164836. https://doi.org/10.1371/journal.pone.0164836.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Shi W, Qin M, Chen F, Xia B. Supragingival microbial profiles of permanent and deciduous teeth in children with mixed dentition. PLoS ONE. 2016;11:e0146938. https://doi.org/10.1371/journal.pone.0146938.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Murayama Y, Nagai A, Okamura K, Kurihara H, Nomura Y, Kokeguchi S, et al. Serum immunoglobulin G antibody to periodontal bacteria. Adv Dent Res. 1988;2:339–45. https://doi.org/10.1177/08959374880020022401.

    Article  PubMed  Google Scholar 

  38. Sugi N, Naruishi K, Kudo C, Hisaeda-Kako A, Kono T, Maeda H, Takashiba S. Prognosis of periodontitis recurrence after intensive periodontal treatment using examination of serum IgG antibody titer against periodontal bacteria. J Clin Lab Anal. 2011;25:25–322.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Wang J, Qi J, Zhao H, He S, Zhang Y, Wei S, et al. Metagenomic sequencing reveals microbiota and its functional potential associated with periodontal disease. Sci Rep. 2013;3:1843. https://doi.org/10.1038/srep01843.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Takeshita T, Matsuo K, Furuta M, Shibata Y, Fukami K, Shimazaki Y, et al. Distinct composition of the oral indigenous microbiota in South Korean and Japanese adults. Sci Rep. 2014;4:6990. https://doi.org/10.1038/srep06990.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Socransky SS, Smith C, Haffajee AD. Subgingival microbial profiles in refractory periodontal disease. J Clin Periodontol. 2002;29:260–8.

    Article  PubMed  Google Scholar 

  42. Page RC, Kornman KS. The pathogenesis of human periodontitis: an introduction. Periodontol. 2000;1997(14):9–11.

    Google Scholar 

  43. Takeshita T, Nakano Y, Kumagai T, Yasui M, Kamio N, Shibata Y, et al. The ecological proportion of indigenous bacterial populations in saliva is correlated with oral health status. ISME J. 2009;3:65–78. https://doi.org/10.1038/ismej.2008.91.

    Article  PubMed  Google Scholar 

  44. Pérez-Chaparro PJ, Gonçalves C, Figueiredo LC, Faveri M, Lobão E, Tamashiro N, et al. Newly identified pathogens associated with periodontitis: a systematic review. J Dent Res. 2014;93:846–58. https://doi.org/10.1177/0022034514542468.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Khlgatian M, Nassar H, Chou HH, Gibson FC, Genco CA. Fimbria-dependent activation of cell adhesion molecule expression in Porphyromonas gingivalis-infected endothelial cells. Infect Immun. 2002;70:257–67.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Imamura T, Travis J, Potempa J. The biphasic virulence activities of gingipains: activation and inactivation of host proteins. Curr Protein Pept Sci. 2003;4:443–50.

    Article  PubMed  Google Scholar 

  47. Toyofuku T, Inoue Y, Kurihara N, Kudo T, Jibiki M, Sugano N, et al. Differential detection rate of periodontopathic bacteria in atherosclerosis. Surg Today. 2011;41:1395–400. https://doi.org/10.1007/s00595-010-4496-5.

    Article  PubMed  Google Scholar 

  48. Jain A, Batista EL, Serhan C, Stahl GL, Van Dyke TE. Role for periodontitis in the progression of lipid deposition in an animal model. Infect Immun. 2003;71:6012–8 (PubMed PMID: 14500522; PubMed Central PMCID: PMCPMC201045).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Koren O, Spor A, Felin J, Fåk F, Stombaugh J, Tremaroli V, et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci USA. 2011;108:4592–8. https://doi.org/10.1073/pnas.1011383107.

    Article  PubMed  Google Scholar 

  50. Tsutsui H, Imamura M, Fujimoto J, Nakanishi K. The TLR4/TRIF-mediated activation of NLRP3 inflammasome underlies endotoxin-induced liver injury in mice. Gastroenterol Res Pract. 2010;2010:641865. https://doi.org/10.1155/2010/641865.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575–84. https://doi.org/10.1056/NEJMoa1109400.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank all the staff in the Department of Biobank, Okayama University Hospital for helping our research development. We also wish to acknowledge all the department staff at the Department of Pathophysiology-Periodontal Science of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences for supporting this study.

Funding

This study was supported by the Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences in Okayama, Japan.

Author information

Authors and Affiliations

  1. Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8525, Japan

    Daichi Isoshima, Zulema Arias, Tadashi Yamamoto & Shogo Takashiba

  2. Department of Periodontics and Endodontics, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8525, Japan

    Keisuke Yamashiro, Kazuyuki Matsunaga & Kazuhiro Omori

  3. Department of Neurology, Brain Attack Center Ota Memorial Hospital, 3-6-28 Okinogami-cho, Fukuyama, Hiroshima, 720-0825, Japan

    Kazuyuki Matsunaga, Shinzo Ota, Michiyoshi Sato, Yutaka Shimoe & Tatsuo Kohriyama

  4. Oral Microbiome Center, Taniguchi Dental Clinic, 1-9-14 Tokiwa-cho, Takamatsu, Kagawa, 760-0054, Japan

    Makoto Taniguchi

  5. Okayama University Hospital Biobank, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8525, Japan

    Takehiro Matsubara & Shuta Tomida

  6. Center for Comprehensive Genomic Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8525, Japan

    Shuta Tomida

Authors
  1. Daichi Isoshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keisuke Yamashiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuyuki Matsunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Makoto Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takehiro Matsubara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shuta Tomida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shinzo Ota
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michiyoshi Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yutaka Shimoe
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tatsuo Kohriyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zulema Arias
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kazuhiro Omori
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tadashi Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Shogo Takashiba
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DI performed samples collection, conducted the experimental works, interpreted the results, and wrote the draft manuscript. KY supervised all experiments and edited the manuscript. KM performed the oral examination and sample collection. MT performed co-occurrence analysis. SO, MS, and YS operated patients and collected samples. MT and ST performed NGS analysis. ZA performed English editing for the manuscript. TK, KO, and TY gave professional advises. ST was responsible for the study, and supervised and edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Keisuke Yamashiro.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

This study was approved by the ethics committee of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital (Authorization Number: 1603–059) and Brain Attack Center Ota Memorial Hospital (Authorization Number: 121).

Informed consent

We obtained consents for publication from the participants.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Isoshima, D., Yamashiro, K., Matsunaga, K. et al. Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis. Odontology 109, 239–249 (2021). https://doi.org/10.1007/s10266-020-00524-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10266-020-00524-w

Keywords

Search

Navigation