Abstract
Saliva is a biofluid largely used in metabolomics for the assessment of local and systemic diseases. Our group has previously demonstrated the salivary metabolomic signature of children with dental caries (Fidalgo et al. Metabolomics 9(3):657–666, 2013). The aim of the current study was investigation, using NMR spectroscopy, of the changes observed for metabolite markers for caries lesions before and after dental treatment. Saliva from children with and without dental caries before and after treatment was analyzed by NMR. Partial least squared discriminant analysis (PLS-DA) conducted on the spectroscopic data sets showed a clear separation of saliva metabolic profile of children with and without caries, and multilevel PLS-DA demonstrated difference before and after dental treatment. Our results demonstrate that organic acids are associated with disease activity because their reductions were observed after dental treatment. There was a demonstrated reduction here in the levels of acetate, propionate, fatty acid, butyrate and saccharides. We also observed a drop in the level of microorganisms upon dental treatment. The dental treatment therefore modified the properties of the oral cavity, leading to changes in the salivary profiles after treatment.
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References
AAPD. (2011). Policy on early childhood caries (ECC): Classifications, consequences, and preventive strategies. Pediatric Dentistry, 30(7 Suppl), 40–43.
Aimetti, M., Cacciatore, S., Graziano, A., & Tenori, L. (2012). Metabonomic analysis of saliva reveals generalized chronic periodontitis signature. Metabolomics, 8(3), 465–474.
Bergandi, L., Defabianis, P., Re, F., Preti, G., Aldieri, E., Garetto, S., et al. (2007). Absence of soluble CD14 in saliva of young patients with dental caries. European Journal of Oral Sciences, 115(2), 93–96.
Bertini, I., Luchinat, C., Miniati, M., Monti, S., & Tenori, L. (2014). Phenotyping COPD by 1H NMR metabolomics of exhaled breath condensate. Metabolomics, 10(2), 302–311.
Bertram, H. C., Eggers, N., & Eller, N. (2009). Potential of human saliva for nuclear magnetic resonance-based metabolomics and for health-related biomarker identification. Analytical Chemistry, 81(21), 9188–9193.
Bretz, W. A., Corby, P., Schork, N., & Hart, T. C. (2003). Evidence of a contribution of genetic factors to dental caries risk. Journal of Evidence Based Dental Practice, 3(4), 185–189.
Caufield, P. W., Cutter, G. R., & Dasanayake, A. P. (1993). Initial acquisition of mutans streptococci by infants: evidence for a discrete window of infectivity. Journal of Dental Research, 72(1), 37–45.
Cuevas-Cordoba, B., & Santiago-Garcia, J. (2014). Saliva: A Fluid of Study for OMICS. OMICS: A Journal of Integrative Biology, 18(2), 87–97.
Dawes, C. (1972). Circadian rhythms in human salivary flow rate and composition. Journal of Physiology, 220(3), 529–545.
Deja, S., Dawiskiba, T., Balcerzak, W., Orczyk-Pawilowicz, M., Glod, M., Pawelka, D., et al. (2013). Follicular adenomas exhibit a unique metabolic profile. 1H NMR studies of thyroid lesions. PLoS One, 8(12), e84637.
Fidalgo, T. K. S., Abreu, V., Freitas-Fernandes, L. B., Souza, I. P. R., & Maia, L. C. (2012). Do salivary lipids influence dental caries susceptibility? A systematic review. Open Access Scientific Reports, 1(12), 1–4.
Fidalgo, T. K. S., Ammari, M., Freitas-Fernandes, L. B., Mattos, C. T., Souza, I. P., & Maia, L. C. (2014). The relationship between unspecific s-IgA and dental caries: A systematic review and meta-analysis. Journal of Dentistry. doi:10.1016/j.jdent.2014.07.011.
Fidalgo, T. K. S., Freitas-Fernandes, L. B., Angeli, R., Muniz, A. M. S., Gonsalves, E., Santos, R., et al. (2013). Salivary metabolite signatures of children with and without dental caries lesions. Metabolomics, 9(3), 657–666.
Fiehn, O., Robertson, D., Griffin, J., Werf, M., Nikolau, B., Morrison, N., et al. (2007). The metabolomics standards initiative (MSI). Metabolomics, 3(3), 175–178.
Garcia-Godoy, F., & Hicks, M. J. (2008). Maintaining the integrity of the enamel surface: the role of dental biofilm, saliva and preventive agents in enamel demineralization and remineralization. Journal of the American Dental Association, 139(Suppl), 25S–34S.
Goodacre, R., Broadhurst, D., Smilde, A. K., Kristal, B. S., Baker, J. D., Beger, R., et al. (2007). Proposed minimum reporting standards for data analysis in metabolomics. Metabolomics, 3(3), 231–241.
Grootveld, M., & Silwood, C. J. (2005). 1H NMR analysis as a diagnostic probe for human saliva. Biochemical and Biophysical Research Communication, 329(1), 1–5.
Jolliffe, I. T. (2002). Principal component analysis (2nd ed.). New York: Springer-Verlag.
Law, V., & Seow, W. K. (2007). A longitudinal study of 0.2 % chlorhexidine gel for removal of mutans streptococci infection in preschool children. Australian Dental Journal, 52(1), 26–32.
Li, Y., Navia, J. M., & Caufield, P. W. (1994). Colonization by mutans streptococci in the mouths of 3- and 4-year-old Chinese children with or without enamel hypoplasia. Archives of Oral Biology, 39(12), 1057–1062.
Li, L., Sui, W., Che, W., Li, W., Chen, J., Li, H., et al. (2013). 1H NMR-based metabolic profiling of human serum before and after renal transplantation. ASAIO Journal, 59(3), 286–293.
Martins-Junior, P. A., Vieira-Andrade, R. G., Correa-Faria, P., Oliveira-Ferreira, F., Marques, L. S., & Ramos-Jorge, M. L. (2013). Impact of early childhood caries on the oral health-related quality of life of preschool children and their parents. Caries Research, 47(3), 211–218.
Mattos-Graner, R. O., Smith, D. J., King, W. F., & Mayer, M. P. (2000). Water-insoluble glucan synthesis by mutans streptococcal strains correlates with caries incidence in 12- to 30-month-old children. Journal of Dental Research, 79(6), 1371–1377.
Morou-Bermudez, E., Elias-Boneta, A., Billings, R. J., Burne, R. A., Garcia-Rivas, V., Brignoni-Nazario, V., et al. (2011). Urease activity in dental plaque and saliva of children during a three-year study period and its relationship with other caries risk factors. Archives of Oral Biology, 56(11), 1282–1289.
Neyraud, E., Tremblay-Franco, M., Gregoire, S., & Berdeaux, O. (2013). Relationships between the metabolome and the fatty acid composition of human saliva; effects of stimulation. Metabolomics, 9(1), 213–222.
Ng, D. J. Y., Pasikanti, K. K., & Chan, E. C. Y. (2011). Trend analysis of metabonomics and systematic review of metabonomics-derived cancer marker metabolites. Metabolomics, 7(2), 155–172.
Olszowski, T., Adler, G., Janiszewska-Olszowska, J., Safranow, K., & Kaczmarczyk, M. (2012). MBL2, MASP2, AMELX, and ENAM gene polymorphisms and dental caries in Polish children. Oral Diseases, 18(4), 389–395.
Palmer, C. A., Kent, R, Jr, Loo, C. Y., Hughes, C. V., Stutius, E., Pradhan, N., et al. (2010). Diet and caries-associated bacteria in severe early childhood caries. Journal of Dental Research, 89(11), 1224–1229.
Puchades-Carrasco, L., Lecumberri, R., Martinez-Lopez, J., Lahuerta, J. J., Mateos, M. V., Prosper, F., et al. (2013). Multiple myeloma patients have a specific serum metabolomic profile that changes after achieving complete remission. Clinical Cancer Research, 19(17), 4770–4779.
Ramadan, Z., Jacobs, D., Grigorov, M., & Kochhar, S. (2006). Metabolic profiling using principal component analysis, discriminant partial least squares, and genetic algorithms. Talanta, 68(5), 1683–1691.
Rigante, D., Inzitari, R., Carone, M., Fanali, C., Stabile, A., Cabras, T., et al. (2008). Correspondence between clinical improvement and proteomic changes of the salivary peptide complex in a child with primary Sjogren syndrome. Rheumatology International, 28(8), 801–806.
Seow, W. K., & Wan, A. (2000). A controlled study of the morphometric changes in the primary dentition of pre-term, very-low-birthweight children. Journal of Dental Research, 79(1), 63–69.
Silwood, C. J., Lynch, E., Claxson, A. W., & Grootveld, M. C. (2002). 1H and (13)C NMR spectroscopic analysis of human saliva. Journal of Dental Research, 81(6), 422–427.
Silwood, C. J., Lynch, E. J., Seddon, S., Sheerin, A., Claxson, A. W., & Grootveld, M. C. (1999). 1H NMR analysis of microbial-derived organic acids in primary root carious lesions and saliva. NMR in Biomedicine, 12(6), 345–356.
Slomiany, B. L., Murty, V. L., Mandel, I. D., Zalesna, G., & Slomiany, A. (1989). Physico-chemical characteristics of mucus glycoproteins and lipids of the human oral mucosal mucus coat in relation to caries susceptibility. Archives of Oral Biology, 34(4), 229–237.
Sreebny, L. M., Chatterjee, R., & Kleinberg, I. (1985). Clearance of glucose and sucrose from the saliva of human subjects. Archives of Oral Biology, 30(3), 269–274.
Sugimoto, M., Wong, D. T., Hirayama, A., Soga, T., & Tomita, M. (2010). Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. Metabolomics, 6(1), 78–95.
Szyman´ska, E., van Dorsten, F. A., Troost, J., Paliukhovich, I., van Velzen, E. J. J., Hendriks, M. M. W. B., et al. (2012). A lipidomic analysis approach to evaluate the response to cholesterol-lowering food intake. Metabolomics, 8(5), 894–906.
Takeda, I., Stretch, C., Barnaby, P., Bhatnager, K., Rankin, K., Fu, H., et al. (2009). Understanding the human salivary metabolome. NMR in Biomedicine, 22(6), 577–584.
Tanner, A. C., Kent, R. L, Jr, Holgerson, P. L., Hughes, C. V., Loo, C. Y., Kanasi, E., et al. (2011). Microbiota of severe early childhood caries before and after therapy. Journal of Dental Research, 90(11), 1298–1305.
Tayab, T., Rai, K., & Kumari, A. V. (2012). Evaluating the physicochemical properties and inorganic elements of saliva in caries-free and caries-active children. An in vivo study. European Journal of Paediatric Dentistry, 13(2), 107–112.
Tenuta, L. M., Del Bel Cury, A. A., Bortolin, M. C., Vogel, G. L., & Cury, J. A. (2006). Ca, Pi, and F in the fluid of biofilm formed under sucrose. Journal of Dental Research, 85(9), 834–838.
Van Houte, J., Russo, J., & Prostak, K. S. (1989). Increased pH-lowering ability of S. mutans cell masses associated with extracellular glucan-rich matrix material and the mechanisms involved. Journal of Dental Research, 68(3), 451–459.
Van Nieuw Amerongen, A., Bolscher, J. G., & Veerman, E. C. (2004). Salivary proteins: protective and diagnostic value in cariology? Caries Research, 38(3), 247–253.
van Velzen, E. J. J., Westerhuis, J. A., van Duynhoven, J. P. M., et al. (2008). Multilevel data analysis of a crossover designed human nutritional intervention study. Journal of Proteome Research, 7, 4483–4491.
Wan, A. K., Seow, W. K., Purdie, D. M., Bird, P. S., Walsh, L. J., & Tudehope, D. I. (2003). A longitudinal study of S. mutans colonization in infants after tooth eruption. Journal of Dental Research, 82(7), 504–508.
World Health Organization (WHO). (1997). Oral health surveys: basic methods (4th ed.). Geneva: World Health Organization.
Acknowledgments
The authors acknowledge the financial support from the following agencies: National Institute of Science and Technology of Structural Biology and Bioimaging (INCT-INBEB), CNPq, FAPERJ, FINEP, and CAPES. Also, the authors thank Dr. Ewa Szyman´ska for helping us with the M-PLS-DA Matlab routines.
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Fidalgo, T.K.S., Freitas-Fernandes, L.B., Almeida, F.C.L. et al. Longitudinal evaluation of salivary profile from children with dental caries before and after treatment. Metabolomics 11, 583–593 (2015). https://doi.org/10.1007/s11306-014-0717-z
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DOI: https://doi.org/10.1007/s11306-014-0717-z