Total human saliva is a biofluid which can be considered as a “mirror” reflecting the state of the body’s health. The “spectral mid-infrared fingerprint” represents a snapshot of the intrinsic biomolecular composition of a saliva sample translating multiple information about the patient, and likely to be related not only to his physiopathological status but also to his behavioral habits or even current medical treatments. These different patient-related characteristics are “confounding factors,” which may strongly affect the infrared data of salivary samples and disrupt the search for specific salivary biomarkers in the detection of diseases, especially in the case of complex pathologies influenced by multiple risk factors such as genetic factors and behavioral factors, and also other comorbidities. In this study, dealing with the processing of infrared saliva spectra from 56 patients, our aim was to highlight spectral features associated with some patient characteristics, namely tobacco smoking, periodontal diseases, and gender. By using multivariate statistical methods of feature selection (principal component analysis coupled with Kruskal–Wallis test, linear discriminant analysis coupled with randfeatures function), we were able to identify the discriminant vibrations associated with a specific factor and to assess the related spectral variability. Based on the methodology demonstrated here, it could be very valuable in the future to develop processing aimed at neutralizing these variabilities, in order to determine specific spectroscopic markers related to a multifactorial disease for diagnostic or follow-up purposes.
This is a preview of subscription content, log in to check access.
The authors gratefully acknowledge the Association Française pour la Recherche sur l’Hidrosadénite (AFRH) and the Association Française d’Épargne et de Retraite (AFER).
The authors thank Dr. Marie-Pascale Hippolyte, University Hospital of Reims, for improving the English presentation of this manuscript.
Compliance with ethical standards
This study was approved by the French Ethics Committee for the Protection of Individuals Consenting to Biomedical Research (No. 18019), by the French National Agency for Medicines and Health Products Safety (2018-A0016451), and by ClinicalTrials.gov (NCT03553888).
Conflict of interest
The authors declare that they have no conflict to declare.
Schafer CA, Schafer JJ, Yakob M, Lima P, Camargo P, Wong DTW. Saliva diagnostics: utilizing oral fluids to determine health status. Monogr Oral Sci. 2014;24:88–98.CrossRefGoogle Scholar
Beale D, Jones O, Karpe A, Dayalan S, Oh D, Kouremenos K, et al. A review of analytical techniques and their application in disease diagnosis in breathomics and salivaomics research. Int J Mol Sci. 2016;18:24.CrossRefGoogle Scholar
Kaczor-Urbanowicz KE, Martin Carreras-Presas C, Aro K, Tu M, Garcia-Godoy F, Wong DT. Saliva diagnostics – current views and directions. Exp Biol Med. 2017;242:459–72.CrossRefGoogle Scholar
Wang X, Kaczor-Urbanowicz KE, Wong DTW. Salivary biomarkers in cancer detection. Med Oncol Northwood Lond Engl. 2017;34:7.CrossRefGoogle Scholar
Wang A, Wang C, Tu M, Wong D. Oral biofluid biomarker research: current status and emerging frontiers. Diagnostics. 2016;6:45.CrossRefGoogle Scholar
Lawrence HP. Salivary markers of systemic disease: noninvasive diagnosis of disease and monitoring of general health. J Can Dent Assoc. 2002;68:170–4.Google Scholar
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.CrossRefGoogle Scholar
Kuku G, Saricam M, Akhatova F, Danilushkina A, Fakhrullin R, Culha M. Surface-enhanced Raman scattering to evaluate nanomaterial cytotoxicity on living cells. Anal Chem. 2016;88:9813–20.CrossRefGoogle Scholar
Gowen AA, Feng Y, Gaston E, Valdramidis V. Recent applications of hyperspectral imaging in microbiology. Talanta. 2015;137:43–54.CrossRefGoogle Scholar
Petrich W, Lewandrowski KB, Muhlestein JB, Hammond MEH, Januzzi JL, Lewandrowski EL, et al. Potential of mid-infrared spectroscopy to aid the triage of patients with acute chest pain. Analyst. 2009;134:1092.CrossRefGoogle Scholar
Khaustova S, Shkurnikov M, Tonevitsky E, Artyushenko V, Tonevitsky A. Noninvasive biochemical monitoring of physiological stress by Fourier transform infrared saliva spectroscopy. Analyst. 2010;135:3183.CrossRefGoogle Scholar
Simsek Ozek N, Zeller I, Renaud DE, Gümüş P, Nizam N, Severcan F, et al. Differentiation of chronic and aggressive periodontitis by FTIR spectroscopy. J Dent Res. 2016;95:1472–8.CrossRefGoogle Scholar
Bottoni U, Tiriolo R, Pullano SA, Dastoli S, Amoruso GF, Nistico SP, et al. Infrared saliva analysis of psoriatic and diabetic patients: similarities in protein components. IEEE Trans Biomed Eng. 2016;63:379–84.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Diem M. Comments on recent reports on infrared spectral detection of disease markers in blood components. J Biophotonics. 2018;11:e201800064.CrossRefGoogle Scholar
Caton J G, Armitage G, Berglundh T, Chapple ILC, Jepsen S, Kornman K S, et al. A new classification scheme for periodontal and peri-implant diseases and conditions - introduction and key changes from the 1999 classification. J Clin Periodontol. 2018;45:S1–8.CrossRefGoogle Scholar
Untereiner V, Dhruvananda Sockalingum G, Garnotel R, Gobinet C, Ramaholimihaso F, Ehrhard F, et al. Bile analysis using high-throughput FTIR spectroscopy for the diagnosis of malignant biliary strictures: a pilot study in 57 patients: spectral diagnosis of malignant biliary strictures. J Biophotonics. 2014;7:241–53.CrossRefGoogle Scholar
Helm D, Labischinski H, Naumann D. Elaboration of a procedure for identification of bacteria using Fourier-transform IR spectral libraries: a stepwise correlation approach. J Microbiol Methods. 1991;14:127–42.CrossRefGoogle Scholar
Afseth NK, Kohler A. Extended multiplicative signal correction in vibrational spectroscopy, a tutorial. Chemom Intell Lab Syst. 2012;117:92–9.CrossRefGoogle Scholar
Abdi H, Williams LJ. Principal component analysis: principal component analysis. Wiley Interdiscip Rev Comput Stat. 2010;2:433–59.CrossRefGoogle Scholar
Eklouh-Molinier C, Happillon T, Bouland N, Fichel C, Diébold M-D, Angiboust J-F, et al. Investigating the relationship between changes in collagen fiber orientation during skin aging and collagen/water interactions by polarized-FTIR microimaging. Analyst. 2015;140:6260–8.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Takamura A, Watanabe K, Akutsu T, Ozawa T. Soft and robust identification of body fluid using Fourier transform infrared spectroscopy and chemometric strategies for forensic analysis. Sci Rep. 2018;8:8459.CrossRefGoogle Scholar
Aggarwal A, Keluskar V, Goyal R, Dahiya P. Salivary thiocyanate: a biochemical indicator of cigarette smoking in adolescents. Oral Health Prev Dent. 2013;11:221–7.Google Scholar
Popa C. Infrared spectroscopy study of the influence of inhaled vapors/smoke produced by cigarettes of active smokers. J Biomed Opt. 2014;20:051003.CrossRefGoogle Scholar
Xiang XM, Liu KZ, Man A, Ghiabi E, Cholakis A, Scott DA. Periodontitis-specific molecular signatures in gingival crevicular fluid. J Periodontal Res. 2010;45:345–52.CrossRefGoogle Scholar
Panjamurthy K, Manoharan S, Ramachandran CR. Lipid peroxidation and antioxidant status in patients with periodontitis. Cell Mol Biol Lett. 2005;10:255–64.Google Scholar
Clifton S, Macdowall W, Copas AJ, Tanton C, Keevil BG, Lee DM, et al. Salivary testosterone levels and health status in men and women in the British general population: findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). J Clin Endocrinol Metab. 2016;101:3939–51.CrossRefGoogle Scholar
Muro CK, de Souza Fernandes L, Lednev IK. Sex determination based on Raman spectroscopy of saliva traces for forensic purposes. Anal Chem. 2016;88:12489–93.CrossRefGoogle Scholar
Miller VM. Why are sex and gender important to basic physiology and translational and individualized medicine? Am J Physiol Heart Circ Physiol. 2014;306:H781–8.CrossRefGoogle Scholar
García-Blanco A, Vento M, Diago V, Cháfer-Pericás C. Reference ranges for cortisol and α-amylase in mother and newborn saliva samples at different perinatal and postnatal periods. J Chromatogr B Anal Technol Biomed Life Sci. 2016;1022:249–55.CrossRefGoogle Scholar
Steiner G, Bartels T, Stelling A, Krautwald-Junghanns M-E, Fuhrmann H, Sablinskas V, et al. Gender determination of fertilized unincubated chicken eggs by infrared spectroscopic imaging. Anal Bioanal Chem. 2011;400:2775–82.CrossRefGoogle Scholar
Chee B, Park B, Bartold PM. Periodontitis and type II diabetes: a two-way relationship. Int J Evid Based Healthc. 2013;11:317–29.CrossRefGoogle Scholar
Kohorst JJ, Kimball AB, Davis MDP. Systemic associations of hidradenitis suppurativa. J Am Acad Dermatol. 2015;73:S27–35.CrossRefGoogle Scholar