Clinical Oral Investigations

, Volume 21, Issue 2, pp 665–674 | Cite as

Persistence of Porphyromonas gingivalis is a negative predictor in patients with moderate to severe periodontitis after nonsurgical periodontal therapy

  • Sigrun Eick
  • Ayse Mathey
  • Karolin Vollroth
  • Martin Kramesberger
  • Walter Bürgin
  • Anton Sculean
  • Christoph Ramseier
  • Holger Jentsch
Original Article
First Online:
Received:
Accepted:

Abstract

Objectives

The aim of this study was to evaluate the quality of prediction for stable results after nonsurgical periodontal therapy by several microbiological variables of the subgingival biofilm and biomarkers of gingival crevicular fluid or oral lavage.

Material and methods

Forty-six individuals with moderate or severe chronic periodontitis receiving nonsurgical periodontal therapy were monitored for clinical variables, selected microorganisms, and biomarkers at baseline and 3 and 6 months thereafter. Logistic regression analysis and general linear model (GLM) were applied for analysis of variance and covariance.

Results

At 6 months, 20 patients showed a high response (HR) to treatment (at least 60 % of reduction of numbers of sites with PD >4 mm), whereas 26 did not (low response, LR). All clinical variables were significantly improved at 3 and 6 months within each group (p < 0.001, each compared with baseline). Modeling the impact of Porphyromonas gingivalis, Treponema denticola, and median of MMP-8 on to the response to treatment as continuous variables by GLM showed a significant influence of these variables (p = 0.045) with the strongest influence of P. gingivalis (p = 0.012) followed by T. denticola (p = 0.045) and no association with MMP-8 (p = 0.982). Samples tested positively for P. gingivalis decreased only in HR (3 months: p = 0.003; 6 months: p = 0.002). Calprotectin levels in GCF were lower in the HR group compared with the LR group at 3 months (p = 0.008) and at 6 months (p = 0.018).

Conclusion

Persistence of P. gingivalis combined with a high GCF level of calprotectin may have a negative predictive value on response to periodontal therapy.

Clinical relevance

Microbiological diagnostics for P. gingivalis before and 3 months after SRP may have a predictive value on response to periodontal therapy. The combination with MMP-8 in oral lavage or preferably calprotectin in GCF might give additional information.

Keywords

Chronic periodontitis Response to treatment Biomarkers Microbiological diagnostics Porphyromonas gingivalis 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

The authors are grateful to Stéphanie Larti, Anna Magdon, and Marianne Weibel (University of Bern, Department of Periodontology, Laboratory of Oral Microbiology) for the technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

The study was funded by the participating departments, by Hain Lifescience, Nehren, Germany, along with a grant from the European Commission (FP7-HEALTH-F3-2012-306029 “TRIGGER”).

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

784_2016_1933_MOESM1_ESM.pdf (74 kb)
ESM 1 (PDF 74 kb)

References

  1. 1.
    Hajishengallis G (2014) Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol 35:3–11. doi: 10.1016/j.it.2013.09.001S1471-4906(13)00145-2 CrossRefPubMedGoogle Scholar
  2. 2.
    Chen H, Jiang W (2014) Application of high-throughput sequencing in understanding human oral microbiome related with health and disease. Front Microbiol 5:508. doi: 10.3389/fmicb.2014.00508 PubMedPubMedCentralGoogle Scholar
  3. 3.
    Socransky SS, Haffajee AD (2005) Periodontal microbial ecology. Periodontol 2000(38):135–187CrossRefGoogle Scholar
  4. 4.
    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 6:1176–1185. doi: 10.1038/ismej.2011.191 CrossRefPubMedGoogle Scholar
  5. 5.
    Nakajima M, Arimatsu K, Kato T, Matsuda Y, Minagawa T, Takahashi N, Ohno H, Yamazaki K (2015) Oral administration of P. gingivalis induces dysbiosis of gut microbiota and impaired barrier function leading to dissemination of enterobacteria to the liver. PLoS One 10:e0134234. doi: 10.1371/journal.pone.0134234 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ng HM, Kin LX, Dashper SG, Slakeski N, Butler CA, Reynolds EC (2015) Bacterial interactions in pathogenic subgingival plaque. Microb Pathog. doi: 10.1016/j.micpath.2015.10.022 PubMedGoogle Scholar
  7. 7.
    Aberg CH, Kelk P, Johansson A (2015) Aggregatibacter actinomycetemcomitans: virulence of its leukotoxin and association with aggressive periodontitis. Virulence 6:188–195. doi: 10.4161/21505594.2014.982428 CrossRefPubMedGoogle Scholar
  8. 8.
    Hajishengallis G (2014) The inflammophilic character of the periodontitis-associated microbiota. Mol Oral Microbiol 29:248–257. doi: 10.1111/omi.12065 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Preshaw PM, Taylor JJ (2011) How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis? J Clin Periodontol 38(Suppl 11):60–84. doi: 10.1111/j.1600-051X.2010.01671.x CrossRefPubMedGoogle Scholar
  10. 10.
    Sapna G, Gokul S, Bagri-Manjrekar K (2014) Matrix metalloproteinases and periodontal diseases. Oral Dis 20:538–550. doi: 10.1111/odi.12159 CrossRefPubMedGoogle Scholar
  11. 11.
    Halperin-Sternfeld M, Levin L (2013) Do we really know how to evaluate tooth prognosis? A systematic review and suggested approach. Quintessence Int 44:447–456. doi: 10.3290/j.qi.a29182 PubMedGoogle Scholar
  12. 12.
    Michalowicz BS, Hodges JS, Pihlstrom BL (2013) Is change in probing depth a reliable predictor of change in clinical attachment loss? J Am Dent Assoc 144:171–178CrossRefPubMedGoogle Scholar
  13. 13.
    Luke R, Khan SN, Iqbal PS, Soman RR, Chakkarayan J, Krishnan V (2015) Estimation of specific salivary enzymatic biomarkers in individuals with gingivitis and chronic periodontitis: a clinical and biochemical study. J Int Oral Health 7:54–57PubMedPubMedCentralGoogle Scholar
  14. 14.
    Ebersole JL, Schuster JL, Stevens J, Dawson D 3rd, Kryscio RJ, Lin Y, Thomas MV, Miller CS (2013) Patterns of salivary analytes provide diagnostic capacity for distinguishing chronic adult periodontitis from health. J Clin Immunol 33:271–279. doi: 10.1007/s10875-012-9771-3 CrossRefPubMedGoogle Scholar
  15. 15.
    Leppilahti JM, Sorsa T, Kallio MA, Tervahartiala T, Emingil G, Han B, Mantyla P (2015) The utility of gingival crevicular fluid matrix metalloproteinase-8 response patterns in prediction of site-level clinical treatment outcome. J Periodontol 86:777–787. doi: 10.1902/jop.2015.140421 CrossRefPubMedGoogle Scholar
  16. 16.
    Charalampakis G, Dahlen G, Carlen A, Leonhardt A (2013) Bacterial markers vs. clinical markers to predict progression of chronic periodontitis: a 2-yr prospective observational study. Eur J Oral Sci 121:394–402. doi: 10.1111/eos.12080 CrossRefPubMedGoogle Scholar
  17. 17.
    Chen W, Cheng YM, Zhang SW, Pan Q (2014) Supervised method for periodontitis phenotypes prediction based on microbial composition using 16S rRNA sequences. Int J Comput Biol Drug Des 7:214–224. doi: 10.1504/IJCBDD.2014.061647 CrossRefPubMedGoogle Scholar
  18. 18.
    Sanchez GA, Miozza VA, Delgado A, Busch L (2013) Salivary IL-1beta and PGE2 as biomarkers of periodontal status, before and after periodontal treatment. J Clin Periodontol 40:1112–1117. doi: 10.1111/jcpe.12164 CrossRefPubMedGoogle Scholar
  19. 19.
    Leppilahti JM, Ahonen MM, Hernandez M, Munjal S, Netuschil L, Uitto VJ, Sorsa T, Mantyla P (2011) Oral rinse MMP-8 point-of-care immuno test identifies patients with strong periodontal inflammatory burden. Oral Dis 17:115–122. doi: 10.1111/j.1601-0825.2010.01716.x CrossRefPubMedGoogle Scholar
  20. 20.
    Ramseier CA, Kinney JS, Herr AE, Braun T, Sugai JV, Shelburne CA, Rayburn LA, Tran HM, Singh AK, Giannobile WV (2009) Identification of pathogen and host-response markers correlated with periodontal disease. J Periodontol 80:436–446. doi: 10.1902/jop.2009.080480 CrossRefPubMedGoogle Scholar
  21. 21.
    Kinney JS, Ramseier CA, Giannobile WV (2007) Oral fluid-based biomarkers of alveolar bone loss in periodontitis. Ann N Y Acad Sci 1098:230–251CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Soder B, Airila Mansson S, Soder PO, Kari K, Meurman J (2006) Levels of matrix metalloproteinases-8 and -9 with simultaneous presence of periodontal pathogens in gingival crevicular fluid as well as matrix metalloproteinase-9 and cholesterol in blood. J Periodontal Res 41:411–417CrossRefPubMedGoogle Scholar
  23. 23.
    Kinney JS, Morelli T, Braun T, Ramseier CA, Herr AE, Sugai JV, Shelburne CE, Rayburn LA, Singh AK, Giannobile WV (2011) Saliva/pathogen biomarker signatures and periodontal disease progression. J Dent Res 90:752–758CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontology / Am Acad Periodontol 4:1–6CrossRefGoogle Scholar
  25. 25.
    Griffiths GS (2003) Formation, collection and significance of gingival crevice fluid. Periodontology 2000(31):32–42CrossRefGoogle Scholar
  26. 26.
    Lange DE, Plagmann HC, Eenboom A, Promesberger A (1977) Clinical methods for the objective evaluation of oral hygiene. Dtsch Zahnarztl Z 32:44–47PubMedGoogle Scholar
  27. 27.
    Eick S, Straube A, Guentsch A, Pfister W, Jentsch H (2011) Comparison of real-time polymerase chain reaction and DNA-strip technology in microbiological evaluation of periodontitis treatment. Diagn Microbiol Infect Dis 69:12–20CrossRefPubMedGoogle Scholar
  28. 28.
    Yang JL, Wang MS, Cheng AC, Pan KC, Li CF, Deng SX (2008) A simple and rapid method for extracting bacterial DNA from intestinal microflora for ERIC-PCR detection. World J Gastroenterol 14:2872–2876CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Cionca N, Giannopoulou C, Ugolotti G, Mombelli A (2009) Amoxicillin and metronidazole as an adjunct to full-mouth scaling and root planing of chronic periodontitis. J Periodontol 80:364–371. doi: 10.1902/jop.2009.080540 CrossRefPubMedGoogle Scholar
  30. 30.
    Suvan J, Petrie A, Moles DR, Nibali L, Patel K, Darbar U, Donos N, Tonetti M, D’Aiuto F (2014) Body mass index as a predictive factor of periodontal therapy outcomes. J Dent Res 93:49–54. doi: 10.1177/0022034513511084 CrossRefPubMedCentralGoogle Scholar
  31. 31.
    (2013) SAS Institute Inc. SAS/STAT® User’s Guide. Version 9.4. SAS Institute Inc., Cary, NCGoogle Scholar
  32. 32.
    Moher D, Schulz KF, Altman DG (2001) The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 357:1191–1194CrossRefPubMedGoogle Scholar
  33. 33.
    Lang NP, Tonetti MS (2003) Periodontal risk assessment (PRA) for patients in supportive periodontal therapy (SPT). Oral Health Prev Dent 1:7–16PubMedGoogle Scholar
  34. 34.
    Lang NP, Suvan JE, Tonetti MS (2015) Risk factor assessment tools for the prevention of periodontitis progression a systematic review. J Clin Periodontol 42(Suppl 16):S59–S70. doi: 10.1111/jcpe.12350 CrossRefPubMedGoogle Scholar
  35. 35.
    Badersten A, Nilveus R, Egelberg J (1981) Effect of nonsurgical periodontal therapy. I Moderately advanced periodontitis. J Clin Periodontol 8:57–72CrossRefPubMedGoogle Scholar
  36. 36.
    Eke PI, Wei L, Thornton-Evans GO, Borrell LN, Borgnakke WS, Dye B and Genco RJ (2016) Risk indicators for periodontitis in US adults: National Health and Nutrition Examination Survey (NHANES) 2009 - 2012. J Periodontol:1-18. doi: 10.1902/jop.2016.160013
  37. 37.
    Bunaes DF, Lie SA, Enersen M, Aastrom AN, Mustafa K, Leknes KN (2015) Site-specific treatment outcome in smokers following non-surgical and surgical periodontal therapy. J Clin Periodontol 42:933–942. doi: 10.1111/jcpe.12462 CrossRefPubMedGoogle Scholar
  38. 38.
    Wan CP, Leung WK, Wong MC, Wong RM, Wan P, Lo EC, Corbet EF (2009) Effects of smoking on healing response to non-surgical periodontal therapy: a multilevel modelling analysis. J Clin Periodontol 36:229–239. doi: 10.1111/j.1600-051X.2008.01371.x CrossRefPubMedGoogle Scholar
  39. 39.
    Stratul SI, Sculean A, Rusu D, Didilescu A, Kasaj A, Jentsch H (2011) Effect of smoking on the results of a chlorhexidine digluconate treatment extended up to 3 months after scaling and root planing-a pilot study. Quintessence Int 42:555–563PubMedGoogle Scholar
  40. 40.
    Farina R, Simonelli A, Rizzi A, Trombelli L (2010) Effect of smoking status on pocket probing depth and bleeding on probing following non-surgical periodontal therapy. Minerva Stomatol 59:1–12PubMedGoogle Scholar
  41. 41.
    Joss A, Adler R, Lang NP (1994) Bleeding on probing. A parameter for monitoring periodontal conditions in clinical practice. J Clin Periodontol 21:402–408CrossRefPubMedGoogle Scholar
  42. 42.
    Kurgan S, Fentoglu O, Onder C, Serdar M, Eser F, Tatakis DN, Gunhan M (2015) The effects of periodontal therapy on gingival crevicular fluid matrix metalloproteinase-8, interleukin-6 and prostaglandin E levels in patients with rheumatoid arthritis. J Periodontal Res. doi: 10.1111/jre.12337 Google Scholar
  43. 43.
    Tester AM, Cox JH, Connor AR, Starr AE, Dean RA, Puente XS, Lopez-Otin C, Overall CM (2007) LPS responsiveness and neutrophil chemotaxis in vivo require PMN MMP-8 activity. PLoS One 2:e312. doi: 10.1371/journal.pone.0000312 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Romanelli R, Mancini S, Laschinger C, Overall CM, Sodek J, McCulloch CA (1999) Activation of neutrophil collagenase in periodontitis. Infect Immun 67:2319–2326PubMedPubMedCentralGoogle Scholar
  45. 45.
    Nakamura T, Kido J, Kido R, Ohishi K, Yamauchi N, Kataoka M, Nagata T (2000) The association of calprotectin level in gingival crevicular fluid with gingival index and the activities of collagenase and aspartate aminotransferase in adult periodontitis patients. J Periodontol 71:361–367. doi: 10.1902/jop.2000.71.3.361 CrossRefPubMedGoogle Scholar
  46. 46.
    Becerik S, Afacan B, Ozturk VO, Atmaca H, Emingil G (2011) Gingival crevicular fluid calprotectin, osteocalcin and cross-linked N-terminal telopeptid levels in health and different periodontal diseases. Dis Markers 31:343–352. doi: 10.3233/DMA-2011-0849 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Zhou M, Meng HX, Zhao YB, Chen ZB (2012) Changes of four proinflammatory proteins in whole saliva during experimental gingivitis. Chin J Dent Res 15:121–127PubMedGoogle Scholar
  48. 48.
    Bevilacqua L, Eriani J, Serroni I, Liani G, Borelli V, Castronovo G, Di Lenarda R (2012) Effectiveness of adjunctive subgingival administration of amino acids and sodium hyaluronate gel on clinical and immunological parameters in the treatment of chronic periodontitis. Ann Stomatol (Roma) 3:75–81Google Scholar
  49. 49.
    Verstappen J, Von den Hoff JW (2006) Tissue inhibitors of metalloproteinases (TIMPs): their biological functions and involvement in oral disease. J Dent Res 85:1074–1084CrossRefPubMedGoogle Scholar
  50. 50.
    Ramseier CA, Eick S, Bronnimann C, Buser D, Bragger U, Salvi GE (2016) Host-derived biomarkers at teeth and implants in partially edentulous patients. A 10-year retrospective study. Clin Oral Implants Res 27:211–217. doi: 10.1111/clr.12566 CrossRefPubMedGoogle Scholar
  51. 51.
    Tuter G, Kurtis B, Serdar M (2002) Effects of phase I periodontal treatment on gingival crevicular fluid levels of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1. J Periodontol 73:487–493. doi: 10.1902/jop.2002.73.5.487 CrossRefPubMedGoogle Scholar
  52. 52.
    Colombo AP, Bennet S, Cotton SL, Goodson JM, Kent R, Haffajee AD, Socransky SS, Hasturk H, Van Dyke TE, Dewhirst FE, Paster BJ (2012) Impact of periodontal therapy on the subgingival microbiota of severe periodontitis: comparison between good responders and individuals with refractory periodontitis using the human oral microbe identification microarray. J Periodontol 83:1279–1287. doi: 10.1902/jop.2012.110566 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Tong KS, Zee KY, Lee DH, Corbet EF (2003) Clinical responses to mechanical periodontal treatment in Chinese chronic periodontitis patients with and without Actinobacillus actinomycetemcomitans. J Periodontol 74:1582–1588. doi: 10.1902/jop.2003.74.11.1582 CrossRefPubMedGoogle Scholar
  54. 54.
    Cionca N, Giannopoulou C, Ugolotti G, Mombelli A (2010) Microbiologic testing and outcomes of full-mouth scaling and root planing with or without amoxicillin/metronidazole in chronic periodontitis. J Periodontol 81:15–23. doi: 10.1902/jop.2009.090390 CrossRefPubMedGoogle Scholar
  55. 55.
    Shiloah J, Patters MR, Dean JW 3rd, Bland P, Toledo G (1998) The prevalence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteroides forsythus in humans 1 year after 4 randomized treatment modalities. J Periodontol 69:1364–1372. doi: 10.1902/jop.1998.69.12.1364 CrossRefPubMedGoogle Scholar
  56. 56.
    Byrne SJ, Dashper SG, Darby IB, Adams GG, Hoffmann B, Reynolds EC (2009) Progression of chronic periodontitis can be predicted by the levels of Porphyromonas gingivalis and Treponema denticola in subgingival plaque. Oral Microbiol Immunol 24:469–477. doi: 10.1111/j.1399-302X.2009.00544.xOMI544 [pii]CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Periodontology, School of Dental MedicineUniversity of BernBernSwitzerland
  2. 2.Centre for Periodontology, Department of Cariology, Endodontology and PeriodontologyUniversity Hospital of LeipzigLeipzigGermany
  3. 3.Ressort Research, School of Dental MedicineUniversity of BernBernSwitzerland

Personalised recommendations