Skip to main content

Advertisement

SpringerLink
Log in

Microbiota present in combined endodontic-periodontal diseases and its risks for endocarditis

  • Research
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Introduction

Infective endocarditis (IE) is an inflammatory disease usually caused by bacteria that enter the bloodstream and establish infections in the inner linings or valves of the heart, including blood vessels. Despite the availability of modern antimicrobial and surgical treatments, IE continues to cause substantial morbidity and mortality. Oral microbiota is considered one of the most significant risk factors for IE. The objective of this study was to evaluate the microbiota present in root canal (RC) and periodontal pocket (PP) clinical samples in cases with combined endo-periodontal lesions (EPL) to detect species related to IE using NGS.

Methods

Microbial samples were collected from 15 RCs and their associated PPs, also from 05 RCs with vital pulp tissues (negative control, NC). Genomic studies associated with bioinformatics, combined with structuring of a database (genetic sequences of bacteria reported for infective endocarditis), allowed for the assessment of the microbial community at both sites. Functional prediction was conducted using PICRUSt2.

Results

Parvimonas, Streptococcus, and Enterococcus were the major genera detected in the RCs and PPs. A total of 79, 96, and 11 species were identified in the RCs, PPs, and NCs, respectively. From them, a total of 34 species from RCs, 53 from PPs, and 2 from NCs were related to IE. Functional inference demonstrated that CR and PP microbiological profiles may not be the only risk factors for IE but may also be associated with systemic diseases, including myocarditis, human cytomegalovirus infection, bacterial invasion of epithelial cells, Huntington’s disease, amyotrophic lateral sclerosis, and hypertrophic cardiomyopathy. Additionally, it was possible to predict antimicrobial resistance variants for broad-spectrum drugs, including ampicillin, tetracycline, and macrolides.

Conclusion

Microorganisms present in the combined EPL may not be the only risk factor for IE but also for systemic diseases. Antimicrobial resistance variants for broad-spectrum drugs were inferred based on PICRUSt-2. State-of-the-art sequencing combined with bioinformatics has proven to be a powerful tool for conducting studies on microbial communities and could considerably assist in the diagnosis of serious infections.

Clinical relevance

Few studies have investigated the microbiota in teeth compromised by combined endo-periodontal lesions (EPL), but none have correlated the microbiological findings to any systemic condition, particularly IE, using NGS techniques. In such cases, the presence of apical periodontitis and periodontal disease can increase IE risk in susceptible patients.

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

References

  1. Carinci F, Martinelli M, Contaldo M et al (2018) Focus on periodontal disease and development of endocarditis. J Biol Regul Homeost Agents 32:143–147

    PubMed  Google Scholar 

  2. Dajani AS, Taubert KA, Wilson W et al (1997) Prevention of bacterial endocarditis. Recommendations by the American Heart Association. JAMA 277:1794–1801

    Article  PubMed  Google Scholar 

  3. Gomez CA, Gerber DA, Zambrano E et al (2015) First case of infectious endocarditis caused by Parvimonas micra. Anaerobe 36:53–55. https://doi.org/10.1016/j.anaerobe.2015.10.007

    Article  PubMed  Google Scholar 

  4. Morris NA, Matiello M, Lyons JL, Samuels MA (2014) Neurologic complications in infective endocarditis: identification, management, and impact on cardiac surgery. Neurohospitalist 4:213–222. https://doi.org/10.1177/1941874414537077

    Article  PubMed  PubMed Central  Google Scholar 

  5. Seymour RA, Lowry R, Whitworth JM, Martin MV (2000) Infective endocarditis, dentistry and antibiotic prophylaxis; time for a rethink? Br Dent J 189:610–616. https://doi.org/10.1038/sj.bdj.4800845

    Article  PubMed  Google Scholar 

  6. Debelian GJ, Olsen I, Tronstad L (1994) Systemic diseases caused by oral microorganisms. Dent Traumatol 10:57–65. https://doi.org/10.1111/j.1600-9657.1994.tb00061.x

    Article  Google Scholar 

  7. Habib G, Lancellotti P, Antunes MJ et al (2015) 2015 ESC Guidelines for the management of infective endocarditis: the task force for the management of infective endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 36:3075–3128. https://doi.org/10.1093/eurheartj/ehv319

    Article  PubMed  Google Scholar 

  8. O’Connor EA, Cornwallis CK, Hasselquist D et al (2018) The evolution of immunity in relation to colonization and migration. Nat Ecol Evol 2:841–849. https://doi.org/10.1038/s41559-018-0509-3

    Article  PubMed  Google Scholar 

  9. Gomes BPFA, Berber VB, Kokaras AS et al (2015) Microbiomes of endodontic-periodontal lesions before and after chemomechanical preparation. J Endod 41:1975–1984. https://doi.org/10.1016/j.joen.2015.08.022

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kamada N, Chen GY, Inohara N, Núñez G (2013) Control of pathogens and pathobionts by the gut microbiota. Nat Immunol 14:685–690. https://doi.org/10.1038/ni.2608

    Article  PubMed  PubMed Central  Google Scholar 

  11. Berg G, Rybakova D, Fischer D et al (2020) Microbiome definition re-visited: old concepts and new challenges. Microbiome 8:103. https://doi.org/10.1186/s40168-020-00875-0

    Article  PubMed  PubMed Central  Google Scholar 

  12. Martín R, Miquel S, Langella P, Bermúdez-Humarán LG (2014) The role of metagenomics in understanding the human microbiome in health and disease. Virulence 5:413–423. https://doi.org/10.4161/viru.27864

    Article  PubMed  PubMed Central  Google Scholar 

  13. Dahlén G, Pipattanagovit P, Rosling B, Möller ÅJR (1993) A comparison of two transport media for saliva and subgingival samples. Oral Microbiol Immunol 8:375–382. https://doi.org/10.1111/j.1399-302X.1993.tb00614.x

    Article  PubMed  Google Scholar 

  14. Mougeot J-LC, Stevens CB, Cotton SL et al (2016) Concordance of HOMIM and HOMI NGS technologies in the microbiome analysis of clinical samples. J Oral Microbiol 8:30379. https://doi.org/10.3402/jom.v8.30379

    Article  PubMed  Google Scholar 

  15. Lopes EM, Passini MRZ, Kishi LT et al (2021) Interrelationship between the microbial communities of the root canals and periodontal pockets in combined endodontic-periodontal diseases. Microorganisms 9:1925. https://doi.org/10.3390/microorganisms9091925

    Article  PubMed  PubMed Central  Google Scholar 

  16. Andermann T, Antonelli A, Barrett RL, Silvestro D (2022) Estimating alpha, beta, and gamma diversity through deep learning. Front Plant Sci 13:839407. https://doi.org/10.3389/fpls.2022.839407

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chao A, Lee S-M (1992) Estimating the number of classes via sample coverage. J Am Stat Assoc 87:210–217. https://doi.org/10.1080/01621459.1992.10475194

    Article  Google Scholar 

  18. Konopiński MK (2020) Shannon diversity index: a call to replace the original Shannon’s formula with unbiased estimator in the population genetics studies. PeerJ 8:e9391. https://doi.org/10.7717/peerj.9391

    Article  PubMed  PubMed Central  Google Scholar 

  19. Maziarz M, Pfeiffer RM, Wan Y, Gail MH (2018) Using standard microbiome reference groups to simplify beta-diversity analyses and facilitate independent validation. Bioinformatics 34:3249–3257. https://doi.org/10.1093/bioinformatics/bty297

    Article  PubMed  PubMed Central  Google Scholar 

  20. Segata N, Izard J, Waldron L et al (2011) Metagenomic biomarker discovery and explanation. Genome Biol 12:R60. https://doi.org/10.1186/gb-2011-12-6-r60

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chong J, Liu P, Zhou G, Xia J (2020) Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data. Nat Protoc 15:799–821. https://doi.org/10.1038/s41596-019-0264-1

    Article  PubMed  Google Scholar 

  22. Douglas GM, Maffei VJ, Zaneveld JR et al (2020) PICRUSt2 for prediction of metagenome functions. Nat Biotechnol 38:685–688. https://doi.org/10.1038/s41587-020-0548-6

    Article  PubMed  PubMed Central  Google Scholar 

  23. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680. https://doi.org/10.1093/nar/22.22.4673

    Article  PubMed  PubMed Central  Google Scholar 

  24. Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797. https://doi.org/10.1093/nar/gkh340

    Article  PubMed  PubMed Central  Google Scholar 

  25. Soding J (2005) Protein homology detection by HMM-HMM comparison. Bioinformatics 21:951–960. https://doi.org/10.1093/bioinformatics/bti125

    Article  PubMed  Google Scholar 

  26. Kent WJ (2002) BLAT—The BLAST-Like Alignment Tool. Genome Res 12:656–664. https://doi.org/10.1101/gr.229202

    Article  PubMed  PubMed Central  Google Scholar 

  27. Edgar RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26:2460–2461. https://doi.org/10.1093/bioinformatics/btq461

    Article  PubMed  Google Scholar 

  28. Zaura E, Keijser BJ, Huse SM, Crielaard W (2009) Defining the healthy “core microbiome” of oral microbial communities. BMC Microbiol 9:259. https://doi.org/10.1186/1471-2180-9-259

    Article  PubMed  PubMed Central  Google Scholar 

  29. Dewhirst FE, Chen T, Izard J et al (2010) The human oral microbiome. J Bacteriol 192:5002–5017. https://doi.org/10.1128/JB.00542-10

    Article  PubMed  PubMed Central  Google Scholar 

  30. Del Giudice C, Vaia E, Liccardo D et al (2021) Infective endocarditis: a focus on oral microbiota. Microorganisms 9:1218. https://doi.org/10.3390/microorganisms9061218

    Article  PubMed  PubMed Central  Google Scholar 

  31. Thomas C, Minty M, Vinel A et al (2021) Oral microbiota: a major player in the diagnosis of systemic diseases. Diagnostics 11:1376. https://doi.org/10.3390/diagnostics11081376

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kilian M, Chapple ILC, Hannig M et al (2016) The oral microbiome – an update for oral healthcare professionals. Br Dent J 221:657–666. https://doi.org/10.1038/sj.bdj.2016.865

    Article  PubMed  Google Scholar 

  33. Dhadse P, Gattani D, Mishra R (2010) The link between periodontal disease and cardiovascular disease: how far we have come in last two decades? J Indian Soc Periodontol 14:148. https://doi.org/10.4103/0972-124X.75908

    Article  PubMed  PubMed Central  Google Scholar 

  34. Humphrey LL, Fu R, Buckley DI et al (2008) Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis. J Gen Intern Med 23:2079–2086. https://doi.org/10.1007/s11606-008-0787-6

    Article  PubMed  Google Scholar 

  35. Sanz M, Marco del Castillo A, Jepsen S et al (2020) Periodontitis and cardiovascular diseases: consensus report. J Clin Periodontol 47:268–288. https://doi.org/10.1111/jcpe.13189

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kumar PS (2017) From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease: oral microbiome and systemic disease. J Physiol 595:465–476. https://doi.org/10.1113/JP272427

    Article  PubMed  Google Scholar 

  37. Debelian GJ, Olsen I, Tronstad L (1995) Bacteremia in conjunction with endodontic therapy. Dent Traumatol 11:142–149. https://doi.org/10.1111/j.1600-9657.1995.tb00476.x

    Article  Google Scholar 

  38. Debelian GJ, Olsen I, Tronstad L (1998) Anaerobic bacteremia and fungemia in patients undergoing endodontic therapy: an overview. Ann Periodontol 3:281–287. https://doi.org/10.1902/annals.1998.3.1.281

    Article  PubMed  Google Scholar 

  39. Fernández-Hidalgo N, Escolà-Vergé L, Pericàs JM (2020) Enterococcus faecalis endocarditis: what’s next? Future Microbiol 15:349–364. https://doi.org/10.2217/fmb-2019-0247

    Article  PubMed  Google Scholar 

  40. Jordal S, Kittang BR, Salminen P-R et al (2018) Infective endocarditis in Western Norway: a 20-year retrospective survey. Infect Dis 50:757–763. https://doi.org/10.1080/23744235.2018.1482419

    Article  Google Scholar 

  41. Gomes BPFA, Jacinto RC, Montagner F et al (2011) Analysis of the antimicrobial susceptibility of anaerobic bacteria isolated from endodontic infections in brazil during a period of nine years. J Endod 37:1058–1062. https://doi.org/10.1016/j.joen.2011.05.015

    Article  PubMed  Google Scholar 

  42. Pietropaoli D, Del Pinto R, Ferri C et al (2019) Definition of hypertension-associated oral pathogens in NHANES. J Periodontol 90:866–876. https://doi.org/10.1002/JPER.19-0046

    Article  PubMed  Google Scholar 

  43. Yakob M, Söder B, Meurman JH et al (2011) Prevotella nigrescens and Porphyromonas gingivalis are associated with signs of carotid atherosclerosis in subjects with and without periodontitis: periodontal microorganisms and atherosclerosis. J Periodontal Res 46:749–755. https://doi.org/10.1111/j.1600-0765.2011.01398.x

    Article  PubMed  Google Scholar 

  44. Kaplan JB, Ragunath C, Velliyagounder K et al (2004) Enzymatic detachment of Staphylococcus epidermidis biofilms. Antimicrob Agents Chemother 48:2633–2636. https://doi.org/10.1128/AAC.48.7.2633-2636.2004

    Article  PubMed  PubMed Central  Google Scholar 

  45. Freires IA, Avilés-Reyes A, Kitten T et al (2017) Heterologous expression of Streptococcus mutans Cnm in Lactococcus lactis promotes intracellular invasion, adhesion to human cardiac tissues and virulence. Virulence 8:18–29. https://doi.org/10.1080/21505594.2016.1195538

    Article  PubMed  Google Scholar 

  46. Inenaga C, Hokamura K, Nakano K et al (2018) A potential new risk factor for stroke: streptococcus mutans with collagen-binding protein. World Neurosurg 113:e77–e81. https://doi.org/10.1016/j.wneu.2018.01.158

    Article  PubMed  Google Scholar 

  47. Tonomura S, Naka S, Tabata K et al (2019) Relationship between Streptococcus mutans expressing Cnm in the oral cavity and non-alcoholic steatohepatitis: a pilot study. BMJ Open Gastroenterol 6:e000329. https://doi.org/10.1136/bmjgast-2019-000329

    Article  PubMed  PubMed Central  Google Scholar 

  48. Misaki T, Naka S, Hatakeyama R et al (2016) Presence of Streptococcus mutans strains harbouring the cnm gene correlates with dental caries status and IgA nephropathy conditions. Sci Rep 6:36455. https://doi.org/10.1038/srep36455

    Article  PubMed  PubMed Central  Google Scholar 

  49. Tagliabue A, Rappuoli R (2018) Changing priorities in vaccinology: antibiotic resistance moving to the top. Front Immunol 9:1068. https://doi.org/10.3389/fimmu.2018.01068

    Article  PubMed  PubMed Central  Google Scholar 

  50. Nishimura RA, Otto CM, Bonow RO et al (2017) 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 135:e1159–e1195. https://doi.org/10.1161/CIR.0000000000000503

    Article  PubMed  Google Scholar 

  51. Thanavaro KL, Nixon JV (Ian) (2014) Endocarditis 2014: an update. Heart Lung 43:334–337. https://doi.org/10.1016/j.hrtlng.2014.03.009

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by São Paulo Research Foundation (FAPESP 2015/23479-5, 2017/14912-2, 19/14441-8, 2021/13871-6), National Scientific and Technological Development Council (CNPq 303852/2019-4, 421801/2021-2), Coordination for the Improvement of Higher Education Personnel (CAPES Finance Code 001), and Fund for the Support of Education, Research and Extension- State University of Campinas (FAEPEX 2036/17).

Author information

Authors and Affiliations

  1. Division of Endodontics, Department of Restorative Dentistry, Piracicaba Dental School, State University of Campinas–UNICAMP, Av. Limeira 901, Bairro Areao, Piracicaba, São Paulo, 13414-903, Brazil

    Brenda P. F. A. Gomes, Vanessa B. Berber, Vito M. Chiarelli-Neto, Emelly Aveiro, Rafaela C. Chapola, Maicon R. Z. Passini & Erica M. Lopes

  2. Department of Molecular Genetics, The Forsyth Institute, Cambridge, MA, USA

    Tsute Chen

  3. Microbiology Department, The Forsyth Institute, Cambridge, MA, USA

    Bruce J. Paster

Authors
  1. Brenda P. F. A. Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vanessa B. Berber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vito M. Chiarelli-Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Emelly Aveiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rafaela C. Chapola
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maicon R. Z. Passini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Erica M. Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tsute Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bruce J. Paster
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: Brenda P. F. A. Gomes. Methodology: Brenda P. F. A. Gomes, Vanessa B. Berber, Rafaela C. Chapola, Vito M. Chiarelli-Neto, Emelly Aveiro, Maicon R. Z. Passini, Erica M Lopes, Tsute Chen, and Bruce J. Paster. Validation: Brenda P. F. A. Gomes, Vanessa B. Berber, Rafaela C. Chapola, Vito M. Chiarelli-Neto, Emelly Aveiro, Maicon R. Z. Passini, Erica M. Lopes, Tsute Chen, and Bruce J. Paster. Formal analysis: Brenda P. F. A. Gomes, Vanessa B. Berber, Rafaela C. Chapola, Vito M. Chiarelli-Neto, Emelly Aveiro, Maicon R. Z. Passini, Erica M. Lopes, Tsute Chen, and Bruce J. Paster. Investigation: Brenda P. F. A. Gomes, Vanessa B. Berber, Rafaela C. Chapola, Vito M. Chiarelli-Neto, Emelly Aveiro, Maicon R. Z. Passini, Erica M. Lopes, Tsute Chen, and Bruce J. Paster. Resources: Brenda P. F. A. Gomes. Data curation: Brenda P. F. A. Gomes, Vanessa B. Berber, Rafaela C. Chapola, Vito M. Chiarelli-Neto, Emelly Aveiro, Maicon R. Z. Passini, Erica M. Lopes, Tsute Chen, and Bruce J. Paster. Writing—original draft: Brenda P. F. A. Gomes, Vanessa B. Berber, Rafaela C. Chapola, Vito M. Chiarelli-Neto, Emelly Aveiro, Maicon R. Z. Passini, Erica M. Lopes, Tsute Chen, and Bruce J. Paster. Writing—review and editing preparation: Brenda P. F. A. Gomes, Vanessa B. Berber, Rafaela C. Chapola, Vito M. Chiarelli-Neto, Emelly Aveiro, Maicon R. Z. Passini, Erica M. Lopes, Tsute Chen, and Bruce J. Paster. Visualization: Brenda P. F. A. Gomes, Vanessa B. Berber, Rafaela C. Chapola, Vito M. Chiarelli-Neto, Emelly Aveiro, Maicon R. Z. Passini, Erica M. Lopes, Tsute Chen, and Bruce J. Paster. Project administration: Brenda P. F. A. Gomes, Vanessa B. Berber, Rafaela C. Chapola, Vito M. Chiarelli-Neto, Emelly Aveiro, Maicon R. Z. Passini, Erica M. Lopes, Tsute Chen, and Bruce J. Paster. Funding acquisition: Brenda P. F. A. Gomes.

Corresponding author

Correspondence to Brenda P. F. A. Gomes.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

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

Consent to participate

For this type of study, formal consent is not required. Informed consent was obtained from all individual participants included in the study.

Conflict of interests

The authors declare no competing interests.

Additional information

Publisher's note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gomes, B.P.F.A., Berber, V.B., Chiarelli-Neto, V.M. et al. Microbiota present in combined endodontic-periodontal diseases and its risks for endocarditis. Clin Oral Invest 27, 4757–4771 (2023). https://doi.org/10.1007/s00784-023-05104-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-023-05104-0

Keywords

Search

Navigation