Advertisement

EPMA Journal

, Volume 9, Issue 2, pp 195–203 | Cite as

Pathology-specific molecular profiles of saliva in patients with multiple dental caries—potential application for predictive, preventive and personalised medical services

  • Pavel Seredin
  • Dmitry Goloshchapov
  • Yuri Ippolitov
  • Pimm Vongsvivut
Research

Abstract

Background

Improving the quality of life is part of the global agenda. The focus is predominantly on prevention of socially significant diseases. Combating dental caries-related diseases is a top priority as it has a huge impact on people’s social lives. Therefore, the purpose of the work was to study the changes in the molecular composition of saliva from subjects with multiple caries lesions using spectroscopic methods of analysis to identify potential tissue markers of caries development for predictive, preventive and personalised medical services.

Objectives and methods

The molecular composition of mixed saliva (oral fluid) from subjects with and without multiple caries was analysed with the use of spectroscopic techniques, FTIR with synchrotron radiation for the excitation. The IR spectra of the oral fluid as well as the calculated mineral-organic, carbon-phosphate, Amide II/Amide I and protein/thiocyanate ratios were compared between subjects with and without multiple caries.

Results

This complex analysis of the obtained experimental data determined that the molecular composition of the oral fluid from those with multiple caries differed from those without caries; the organic-mineral balance in the oral fluid of those with multiple caries shifted towards a reduction in the mineral complexes, accompanied by an increase in the organic component. The thiocyanate content increased more than twofold, accompanied by increased carboxyl groups of esters, lipids and carbohydrates.

Conclusion

The detected features in the IR spectra of mixed saliva as well as the calculated changes in the ratios between organic and inorganic components can be used as biomarkers of cariogenesis in the oral cavity, as a diagnostic criterion in the analysis of the oral fluid samples.

Keywords

Predictive Preventive Personalised medical service FTIR spectroscopy Molecular composition Biomarkers Thiocyanate level 

Notes

Acknowledgements

The part of this research was undertaken with The Infrared Microspectroscopy (IRM) beamline at the Australian Synchrotron.

Authors’ contributions

P.S: conceived and designed the experiments, analysed the data, performed the experiments, contributed reagents/materials/analysis tools, wrote the manuscript

D.G: contributed reagents/materials/analysis tools, analysed the data, prepared the figures and/or tables, wrote the manuscript

Y.I: contributed reagents/materials/analysis tools, wrote the manuscript

P.V: performed the experiments

Funding

This work was supported by the grant of Russian Science Foundation, grant number 16-15-00003.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Ethics approval and consent to participate

All patients whose data were used within the created survey had signed institutional consent for the participation research. All persons who participated in the survey signed written consent. Voronezh State University Ethics Committee approved this study (approval number 001.018-2017). The study was carried out in accordance with the approved guidelines.

References

  1. 1.
    Golubnitschaja O, Baban B, Boniolo G, Wang W, Bubnov R, Kapalla M, et al. Medicine in the early twenty-first century: paradigm and anticipation—EPMA position paper 2016. EPMA J. 2016;7:23.  https://doi.org/10.1186/s13167-016-0072-4.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Golubnitschaja O, Costigliola V,  EPMA. General report & recommendations in predictive, preventive and personalised medicine 2012: white paper of the European Association for Predictive, Preventive and Personalised Medicine. EPMA J. 2012;3.  https://doi.org/10.1186/1878-5085-3-14.
  3. 3.
    Einhorn L, Krapfenbauer K. HTRF: a technology tailored for biomarker determination—novel analytical detection system suitable for detection of specific autoimmune antibodies as biomarkers in nanogram level in different body fluids. EPMA J. 2015;6:23.  https://doi.org/10.1186/s13167-015-0046-y.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lakshmi K, Nelakurthi H, Kumar A, Rudraraju A. Oral fluid-based biosensors: a novel method for rapid and noninvasive diagnosis. Indian J Dent Sci. 2017;9:60.  https://doi.org/10.4103/IJDS.IJDS_6_17.CrossRefGoogle Scholar
  5. 5.
    Pretty IA, Ellwood RP. The caries continuum: opportunities to detect, treat and monitor the re-mineralization of early caries lesions. J Dent. 2013;41(Supplement 2):S12–21.  https://doi.org/10.1016/j.jdent.2010.04.003.CrossRefPubMedGoogle Scholar
  6. 6.
    Kunin AA, Belenova IA, Ippolitov YA, Moiseeva NS, Kunin DA. Predictive research methods of enamel and dentine for initial caries detection. EPMA J. 2013;4:19.  https://doi.org/10.1186/1878-5085-4-19.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Gao X, Jiang S, Koh D, Hsu C-YS. Salivary biomarkers for dental caries. Periodontol 2000. 2016;70:128–41.  https://doi.org/10.1111/prd.12100.CrossRefPubMedGoogle Scholar
  8. 8.
    Baffi M, Almeida Rodrigues J de, Lussi A. Traditional and novel caries detection methods. In: Li M-Y, editor. Contemp. Approach Dent. Caries. InTech; 2012. http://www.intechopen.com/books/contemporary-approach-to-dental-caries/traditional-and-novel-caries-detection-methods
  9. 9.
    Cafiero C, Matarasso S. Predictive, preventive, personalised and participatory periodontology: ‘the 5Ps age’ has already started. EPMA J. 2013;4  https://doi.org/10.1186/1878-5085-4-16.
  10. 10.
    Cova MAMN, Castagnola M, Messana I, Cabras T, Ferreira RMP, Amado FML, et al. Salivary Omics. In: Streckfus CF, editor. Adv. Salivary Diagn. Springer Berlin Heidelberg; 2015. p. 63–82.  https://doi.org/10.1007/978-3-662-45399-5_4.CrossRefGoogle Scholar
  11. 11.
    Yoshizawa JM, Schafer CA, Schafer JJ, Farrell JJ, Paster BJ, Salivary Biomarkers WDTW. Toward future clinical and diagnostic utilities. Clin Microbiol Rev. 2013;26:781–91.  https://doi.org/10.1128/CMR.00021-13.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Nunes LAS, Mussavira S, Bindhu OS. Clinical and diagnostic utility of saliva as a non-invasive diagnostic fluid: a systematic review. Biochem Medica. 2015;25:177–92.  https://doi.org/10.11613/BM.2015.018.CrossRefGoogle Scholar
  13. 13.
    Bottoni U, Tiriolo R, Pullano SA, Dastoli S, Amoruso GF, Nisticò SP, et al. Infrared saliva analysis of psoriatic and diabetic patients: similarities in protein components. IEEE Trans Biomed Eng. 2016;63:379–84.  https://doi.org/10.1109/TBME.2015.2458967.CrossRefPubMedGoogle Scholar
  14. 14.
    Malamud D, Rodriguez-Chavez IR. Saliva as a diagnostic fluid. Dent Clin N Am. 2011;55:159–78.  https://doi.org/10.1016/j.cden.2010.08.004.CrossRefPubMedGoogle Scholar
  15. 15.
    Chiappin S, Antonelli G, Gatti R, De Palo EF. Saliva specimen: a new laboratory tool for diagnostic and basic investigation. Clin Chim Acta. 2007;383:30–40.  https://doi.org/10.1016/j.cca.2007.04.011.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Krapfenbauer K, Drucker E, Thurnher D. Identification of tumour-related proteins as potential screening markers by proteome analysis—protein profiles of human saliva as a predictive and prognostic tool. EPMA J. 2014;5  https://doi.org/10.1186/1878-5085-5-20.
  17. 17.
    Parker F. Applications of infrared spectroscopy in biochemistry, biology, and medicine [Internet]. Springer Science & Business Media; 2012. http://www.springer.com/gp/book/9781468418743
  18. 18.
    Lehtinen J. Spectroscopic studies of human hair, nail, and saliva samples using a cantilever-based photoacoustic detection. Int J Thermophys. 2013;34:1559–68.  https://doi.org/10.1007/s10765-013-1488-x.CrossRefGoogle Scholar
  19. 19.
    Dias C de A. Salivary biomarkers of dental caries [Internet]. Universidade do Porto: Universidade do Porto; 2013. http://repositorio-aberto.up.pt/handle/10216/86159 Google Scholar
  20. 20.
    Gozes I. Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress. EPMA J. 2017;8:255–9.  https://doi.org/10.1007/s13167-017-0110-x.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Fujii S, Sato S, Fukuda K, Okinaga T, Ariyoshi W, Usui M, et al. Diagnosis of periodontal disease from saliva samples using Fourier transform infrared microscopy coupled with partial least squares discriminant analysis. Anal Sci Int J Jpn Soc Anal Chem. 2016;32:225–31.  https://doi.org/10.2116/analsci.32.225.CrossRefGoogle Scholar
  22. 22.
    Almhöjd US, Norén JG, Arvidsson A, Nilsson Å, Lingström P. Analysis of carious dentine using FTIR and ToF-SIMS. Oral Health Dent Manag. 2014;13:735–44.  https://doi.org/10.4172/2247-2452.1000666.PubMedCrossRefGoogle Scholar
  23. 23.
    Armenta S, Garrigues S, de la Guardia M, Brassier J, Alcalà M, Blanco M. Analysis of ecstasy in oral fluid by ion mobility spectrometry and infrared spectroscopy after liquid-liquid extraction. J Chromatogr A 2015;1384:1–8. doi: https://doi.org/10.1016/j.chroma.2015.01.036.
  24. 24.
    Guo L, Shi W. Salivary biomarkers for caries risk assessment. J Calif Dent Assoc. 2013;41:107–18.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Andrade MRTC, Salazar SLA, de Sá LFR, Portela M, Ferreira-Pereira A, Soares RMA, et al. Role of saliva in the caries experience and calculus formation of young patients undergoing hemodialysis. Clin Oral Investig. 2015;19:1–8.  https://doi.org/10.1007/s00784-015-1441-4.CrossRefGoogle Scholar
  26. 26.
    Cunha-Cruz DJ, Scott DJ, Rothen MM, Mancl DL, Lawhorn DT, Brossel DK, et al. Salivary characteristics and dental caries: evidence from general dental practices. J Am Dent Assoc 1939. 2013;144:e31–40. www.ncbi.nlm.nih.gov 23633704CrossRefGoogle Scholar
  27. 27.
    Seredin P, Goloshchapov D, Kashkarov V, Ippolitov Y, Bambery K. The investigations of changes in mineral–organic and carbon–phosphate ratios in the mixed saliva by synchrotron infrared spectroscopy. Results Phys. 2016;6:315–21.  https://doi.org/10.1016/j.rinp.2016.06.005.CrossRefGoogle Scholar
  28. 28.
    Júnior C, Cesar P, Strixino JF, Raniero L, Júnior C, Cesar P, et al. Analysis of saliva by Fourier transform infrared spectroscopy for diagnosis of physiological stress in athletes. Res Biomed Eng. 2015;31:116–24.  https://doi.org/10.1590/2446-4740.0664.CrossRefGoogle Scholar
  29. 29.
    Mikkonen JJW, Raittila J, Rieppo L, Lappalainen R, Kullaa AM, Myllymaa S. Fourier transform infrared spectroscopy and photoacoustic spectroscopy for saliva analysis. Appl Spectrosc. 2016;70:1502–10.  https://doi.org/10.1177/0003702816654149.CrossRefPubMedGoogle Scholar
  30. 30.
    Badea I, Crisan M, Fetea F, Socaciu C. Characterization of resting versus stimulated saliva fingerprints using middle-infrared spectroscopy assisted by principal component analysis. Romanian Biotechnol Lett. 2014;19:9817–27. https://www.rombio.eu/vol19nr6/cuprins.htm Google Scholar
  31. 31.
    Shaw RA, Mantsch HH. Infrared spectroscopy in clinical and diagnostic analysis: Encycl. Anal. Chem, John Wiley & Sons, Ltd; 2006.  https://doi.org/10.1002/9780470027318.a0106.
  32. 32.
    Fried D, Featherstone JDB, Darling CL, Jones RS, Ngaotheppitak P, Bühler CM. Early caries imaging and monitoring with near-infrared light. Dent Clin N Am. 2005;49:771–93, vi.  https://doi.org/10.1016/j.cden.2005.05.008.CrossRefPubMedGoogle Scholar
  33. 33.
    Seredin P, Kashkarov V, Lukin A, Ippolitov Y, Julian R, Doyle S. Local study of fissure caries by Fourier transform infrared microscopy and X-ray diffraction using synchrotron radiation. J Synchrotron Radiat. 2013;20:705–10.  https://doi.org/10.1107/S0909049513019444.CrossRefPubMedGoogle Scholar
  34. 34.
    Liu KZ, Xiang XM, Man A, Sowa MG, Cholakis A, Ghiabi E, et al. In vivo determination of multiple indices of periodontal inflammation by optical spectroscopy. J Periodontal Res. 2009;44:117–24.  https://doi.org/10.1111/j.1600-0765.2008.01112.x.CrossRefPubMedGoogle Scholar
  35. 35.
    Xiang X, Duarte PM, Lima JA, Santos VR, Gonçalves TD, Miranda TS, et al. Diabetes-associated periodontitis molecular features in infrared spectra of gingival crevicular fluid. J Periodontol. 2013;84:1792–800.  https://doi.org/10.1902/jop.2013.120665.CrossRefPubMedGoogle Scholar
  36. 36.
    Rodrigues LM, Magrini TD, Lima CF, Scholz J, da Silva Martinho H, Almeida JD. Effect of smoking cessation in saliva compounds by FTIR spectroscopy. Spectrochim Acta A Mol Biomol Spectrosc. 2017;174:124–9.  https://doi.org/10.1016/j.saa.2016.11.009.CrossRefPubMedGoogle Scholar
  37. 37.
    Orphanou C-M. The detection and discrimination of human body fluids using ATR FT-IR spectroscopy. Forensic Sci Int. 2015;252:e10–6.  https://doi.org/10.1016/j.forsciint.2015.04.020.CrossRefPubMedGoogle Scholar
  38. 38.
    Baker MJ, Hussain SR, Lovergne L, Untereiner V, Hughes C, Lukaszewski RA, et al. Developing and understanding biofluid vibrational spectroscopy: a critical review. Chem Soc Rev. 2016;45:1803–18.  https://doi.org/10.1039/C5CS00585J.CrossRefPubMedGoogle Scholar
  39. 39.
    Rehman IU, Movasaghi Z, Rehman S. Vibrational spectroscopy for tissue analysis [Internet]. 1st ed. Boca Raton: CRC Press; 2012. https://www.crcpress.com/Vibrational-Spectroscopy-for-Tissue-Analysis/Rehman-Movasaghi-Rehman/p/book/9781439836088 CrossRefGoogle Scholar
  40. 40.
    Jeon RJ, Matvienko A, Mandelis A, Abrams SH, Amaechi BT, Kulkarni G. Detection of interproximal demineralized lesions on human teeth in vitro using frequency-domain infrared photothermal radiometry and modulated luminescence. J Biomed Opt. 2007;12:034028.  https://doi.org/10.1117/1.2750289.CrossRefPubMedGoogle Scholar
  41. 41.
    Goloshchapov D, Seredin P, Minakov D, Domashevskaya E. Study of the nanoporous CHAP photoluminiscence for developing the precise methods of early caries detection. IOP Conf Ser Mater Sci Eng. 2018;307:012027.  https://doi.org/10.1088/1757-899X/307/1/012027.CrossRefGoogle Scholar
  42. 42.
    Ismail AI, Sohn W, Tellez M, Amaya A, Sen A, Hasson H, et al. The international caries detection and assessment system (ICDAS): an integrated system for measuring dental caries. Community Dent Oral Epidemiol. 2007;35:170–8.  https://doi.org/10.1111/j.1600-0528.2007.00347.x.CrossRefPubMedGoogle Scholar
  43. 43.
    Seredin P, Goloshchapov D, Prutskij T, Ippolitov Y. Phase transformations in a human tooth tissue at the initial stage of caries. PLoS One. 2015;10:1–11.  https://doi.org/10.1371/journal.pone.0124008.CrossRefGoogle Scholar
  44. 44.
    Pretsch E, Bühlmann P, Badertscher M. IR spectroscopy. Struct. Determ. Org. Compd. Springer, Berlin, Heidelberg; 2009. p. 1–67. doi: https://doi.org/10.1007/978-3-540-93810-1_7, IR Spectroscopy.
  45. 45.
    Lopes J, Correia M, Martins I, Henriques AG, Delgadillo I, da Cruz e Silva O, et al. FTIR and Raman spectroscopy applied to dementia diagnosis through analysis of biological fluids. J Alzheimers Dis. 2016;52:801–12.  https://doi.org/10.3233/JAD-151163.CrossRefPubMedGoogle Scholar
  46. 46.
    Wiercigroch E, Szafraniec E, Czamara K, Pacia MZ, Majzner K, Kochan K, et al. Raman and infrared spectroscopy of carbohydrates: a review. Spectrochim Acta A Mol Biomol Spectrosc. 2017;185:317–35.  https://doi.org/10.1016/j.saa.2017.05.045.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Silverstein RM, Bassler GC, Morrill TC. Spectrometric identification of organic compounds [Internet]. 5th ed. In: Wiley; 1991. https://books.google.ru/books?id=umMvAAAAMAAJ.Google Scholar
  48. 48.
    Scherdin-Almhöjd U. Identification of esters in carious dentine staining and chemo-mechanical excavation [Internet]. 2017. https://gupea.ub.gu.se/handle/2077/51781
  49. 49.
    Elkins KM. Rapid presumptive “fingerprinting” of body fluids and materials by ATR FT-IR spectroscopy*,†. J Forensic Sci. 2011;56:1580–7.  https://doi.org/10.1111/j.1556-4029.2011.01870.x.CrossRefPubMedGoogle Scholar
  50. 50.
    Seredin PV, Goloshchapov DL, Gushchin MS, Ippolitov YA, Prutskij T. The importance of the biomimetic composites components for recreating the optical properties and molecular composition of intact dental tissues. J Phys Conf Ser. 2017;917:042019.  https://doi.org/10.1088/1742-6596/917/4/042019.CrossRefGoogle Scholar
  51. 51.
    Kong J, Yu S. Fourier transform infrared spectroscopic analysis of protein secondary structures. Acta Biochim Biophys Sin. 2007;39:549–59.CrossRefPubMedGoogle Scholar
  52. 52.
    Ihalin R, Loimaranta V, Tenovuo J. Origin, structure, and biological activities of peroxidases in human saliva. Arch Biochem Biophys. 2006;445:261–8.  https://doi.org/10.1016/j.abb.2005.07.004.CrossRefPubMedGoogle Scholar
  53. 53.
    Tenovuo J, Jentsch H, Soukka T, Karhuvaara L. Antimicrobial factors of saliva in relation to dental caries and salivary levels of mutans streptococci. J Biol Buccale. 1992;20:85–90.PubMedGoogle Scholar
  54. 54.
    Baughan LW, Robertello FJ, Sarrett DC, Denny PA, Denny PC. Salivary mucin as related to oral Streptococcus mutans in elderly people. Oral Microbiol Immunol. 2000;15:10–4.CrossRefPubMedGoogle Scholar
  55. 55.
    Larmas M. A chromatographic and histochemical study of nonspecific esterases in human carious dentine. Arch Oral Biol. 1972;17:1121–32.  https://doi.org/10.1016/0003-9969(72)90083-0.CrossRefPubMedGoogle Scholar
  56. 56.
    Gregor Cevc, Theresa M Allen, Saul L Neidleman. Phospholipids handbook [Internet]. CRC press; 1993. https://books.google.ru/books?id=2ZxaucDNWHcC
  57. 57.
    Tomita Y, Miyake N, Yamanaka S. Lipids in human parotid saliva with regard to caries experience. J Oleo Sci. 2008;57:115–21.CrossRefPubMedGoogle Scholar
  58. 58.
    Belstrøm D, Jersie-Christensen RR, Lyon D, Damgaard C, Jensen LJ, Holmstrup P, 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.  https://doi.org/10.7717/peerj.2433.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Avraamova OG, Ippolitov YA, Plotnikova YA, Seredin PV, Goloshapov DV, Aloshina EO. Increased oral fluid remineraling function by endogenous and exogenous saturation methods of its mineral complexes. Stomatologiia (Sofiia). 2017;96:6–11.Google Scholar
  60. 60.
    Seredin PV, Goloshchapov DL, Ippolitov YA, Kalivradzhiyan ES. Does dentifrice provide the necessary saturation of ions in oral fluids to favour remineralisation? Russ Open Med J. 2018;7:e0106.  https://doi.org/10.15275/rusomj.2018.0106.
  61. 61.
    Fiyaz M, Ramesh A, Ramalingam K, Thomas B, Shetty S, Prakash P. Association of salivary calcium, phosphate, pH and flow rate on oral health: a study on 90 subjects. J Indian Soc Periodontol. 2013;17:454–60.  https://doi.org/10.4103/0972-124X.118316.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Rajesh KS, Zareena, Hegde S, Arun Kumar MS. Assessment of salivary calcium, phosphate, magnesium, pH, and flow rate in healthy subjects, periodontitis, and dental caries. Contemp Clin Dent. 2015;6:461–5.  https://doi.org/10.4103/0976-237X.169846.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Schultz CP, Ahmed MK, Dawes C, Mantsch HH. Thiocyanate levels in human saliva: quantitation by Fourier transform infrared spectroscopy. Anal Biochem. 1996;240:7–12.  https://doi.org/10.1006/abio.1996.0323.CrossRefPubMedGoogle Scholar
  64. 64.
    Larsson B, Olivecrona G, Ericson T. Lipids in human saliva. Arch Oral Biol. 1996;41:105–10.CrossRefPubMedGoogle Scholar
  65. 65.
    Hicks J, Garcia-Godoy F, Flaitz C. Biological factors in dental caries: role of saliva and dental plaque in the dynamic process of demineralization and remineralization (part 1). J Clin Pediatr Dent. 2004;28:47–52.  https://doi.org/10.17796/jcpd.28.1.yg6m443046k50u20.CrossRefGoogle Scholar
  66. 66.
    Kirstilä V, Häkkinen P, Jentsch H, Vilja P, Tenovuo J. Longitudinal analysis of the association of human salivary antimicrobial agents with caries increment and cariogenic micro-organisms: a two-year cohort study. J Dent Res. 1998;77:73–80.  https://doi.org/10.1177/00220345980770011101.CrossRefPubMedGoogle Scholar

Copyright information

© European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2018

Authors and Affiliations

  1. 1.Department of Solid State Physics and NanostructuresVoronezh State UniversityVoronezhRussia
  2. 2.Department of Pediatric Dentistry with OrthodontiaVoronezh State Medical UniversityVoronezhRussia
  3. 3.Australian Synchrotron (Synchrotron Light Source Australia Pty LTD)ClaytonAustralia

Personalised recommendations