Journal of the korean academy of Pediatric Dentistry (대한소아치과학회지)

Korean Academy of Pediatric Dentistry (대한소아치과학회)
권호 표지
DOI QR코드

DOI QR Code

Trends in Saliva Research and Biomedical Clinical Applications

타액 연구의 최신 지견과 임상 응용

  • Soyoung Park (Department of Pediatric Dentistry and Dental Research Institute, Pusan National University Dental Hospital) ;
  • Eungyung Lee (Department of Pediatric Dentistry and Dental Research Institute, Pusan National University Dental Hospital) ;
  • Jonghyun Shin (Department of Pediatric Dentistry and Dental Research Institute, Pusan National University Dental Hospital) ;
  • Taesung Jeong (Department of Pediatric Dentistry and Dental Research Institute, Pusan National University Dental Hospital)
  • 박소영 (부산대학교치과병원 소아치과) ;
  • 이은경 (부산대학교치과병원 소아치과) ;
  • 신종현 (부산대학교치과병원 소아치과) ;
  • 정태성 (부산대학교치과병원 소아치과)
  • Received : 2022.12.27
  • Accepted : 2023.01.20
  • Published : 2023.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Function of salivary gland and saliva composition can be an indicator of individual's health status. Recently, saliva has been thought to have a high potential for usage in the biomedical field to diagnose, evaluate, and prevent systemic health due to the technological advances in analyzing and detecting small elements such as immunological and metabolic products, viruses, microorganisms, hormones in saliva. As a diagnostic specimen, saliva has some useful advantages compared to serum. Because of simple non-invasive method, saliva sampling is quite comfort for the patient, and it doesn't require specialists to collect samples. The possibility of infection during the collection process is also low. For this reason, proteins, genetic materials, and various biomarkers in saliva are actively being utilized on studying stress, microbiomics, genetics, and epigenetics. For the research on collecting big data related to systemic health, the needs on biobank has been focused. Regeneration of salivary gland based on tissue engineering has been also on advancement. However, there are still many issues to be solved, such as the standardization of sample collection, storage, and usage. This review focuses on the recent trends in the field of saliva research and highlight the future perspectives in biomedical and other applications.

타액선의 기능과 타액의 구성성분은 개체의 건강 상태를 반영하는 지표가 될 수 있다. 타액에서 바이러스와 미생물, 호르몬, 면역 및 대사산물 등을 검출하는 미량원소 분석기술이 발달함에 따라, 전신건강의 진단, 평가, 예방 분야에서 타액의 활용가능성이 높아지고 있다. 진단 검체로써 타액은 혈액에 비해 채취 방법이 비 침습적이어서 환자의 불편감이 적고 비 전문가에 의한 검체 수집이 가능할 뿐 아니라 채취과정 중 감염 위험성이 낮다는 점에서 장점이 있다. 이러한 이유로 스트레스, 마이크로바이옴, 유전학 및 후생유전학 분야의 연구에 있어 타액 내 단백질, 유전물질이나 각종 생체표지자 등을 활용하는 방법이 주목받고 있다. 또한 전신 건강에 대한 빅데이터 수집 연구와 관련하여 타액을 효율적으로 활용, 보관하기 위한 인체 자원 은행의 필요성이 강조되고 있으며, 조직공학과 접목하여 타액선 재생연구도 활발히 진행되고 있다. 검체 채취법이나 보관, 활용 방법의 표준화를 비롯하여 해결해야 할 과제가 남아있으므로, 본 리뷰에서 타액 및 타액선에 관한 최근의 연구 동향을 알아보고 미래 발전 방향에 대하여 검토해 보고자 하였다.

Keywords

Acknowledgement

We would like to thank Prof. Hyungsik Kim at Department of Life Science in Dentistry (School of Dentistry in Pusan National University) for commenting and informing on organoid of salivary gland. This work was supported by a 2-Year Research Grant of Pusan National University.

References

  1. Fernandes LL, Pacheco VB, Borges L, Athwal HK, de Paula Eduardo F, Bezinelli L, Correa L, Jimenez M, Dame-Teixeira N, Lombaert IMA, Heller D : Saliva in the Diagnosis of COVID-19: A Review and New Research Directions. J Dent Res, 99:1435-1443, 2020.  https://doi.org/10.1177/0022034520960070
  2. Baghizadeh Fini M : Oral saliva and COVID-19. Oral Oncol, 108:104821, 2020. 
  3. Park MS : Salivary diagnostics: saliva-based liquid biopsy. J Korean Acad Geriatr Dent, 13:6-11, 2017. 
  4. Lee JM, Garon E, Wong DT : Salivary diagnostics. Orthod Craniofac Res, 12:206-211, 2009.  https://doi.org/10.1111/j.1601-6343.2009.01454.x
  5. Chiappin S, Antonelli G, Gatti R, De Palo EF : Saliva specimen: a new laboratory tool for diagnostic and basic investigation. Clin Chim Acta, 383:30-40, 2007.  https://doi.org/10.1016/j.cca.2007.04.011
  6. Buczko P, Zalewska A, Szarmach I : Saliva and oxidative stress in oral cavity and in some systemic disorders. J Physiol Pharmacol, 66:3-9, 2015. 
  7. Bhattarai KR, Kim HR, Chae HJ : Compliance with Saliva Collection Protocol in Healthy Volunteers: Strategies for Managing Risk and Errors. Int J Med Sci, 15: 823-831, 2018.  https://doi.org/10.7150/ijms.25146
  8. Miranda-Rius J, Brunet-Llobet L, Lahor-Soler E, Farre M : Salivary Secretory Disorders, Inducing Drugs, and Clinical Management. Int J Med Sci, 12:811-824, 2015.  https://doi.org/10.7150/ijms.12912
  9. Granger DA, Taylor MK : Salivary bioscience: foundations of interdisciplinary saliva research and applications, 1st ed. Springer Nature, Cham, 115-138, 2020. 
  10. Frankiensztajn LM, Elliott E, Koren O : The microbiota and the hypothalamus-pituitary-adrenocortical (HPA) axis, implications for anxiety and stress disorders. Curr Opin Neurobiol, 62:76-82, 2020.  https://doi.org/10.1016/j.conb.2019.12.003
  11. Choi MH : Clinical and Technical Aspects in Free Cortisol Measurement. Endocrinol Metab, 37:599-607, 2022.  https://doi.org/10.3803/EnM.2022.1549
  12. Kirschbaum C, Hellhammer DH : Salivary cortisol in psychoneuroendocrine research: recent developments and applications. Psychoneuroendocrinology, 19:313-333, 1994.  https://doi.org/10.1016/0306-4530(94)90013-2
  13. Buijs RM, van Eden CG, Goncharuk VD, Kalsbeek A : The biological clock tunes the organs of the body: timing by hormones and the autonomic nervous system. J Endocrinol, 177:17-26, 2003.  https://doi.org/10.1677/joe.0.1770017
  14. Wilhelm I, Born J, Kudielka BM, Schlotz W, Wust S : Is the cortisol awakening rise a response to awakening? Psychoneuroendocrinology, 32:358-366, 2007.  https://doi.org/10.1016/j.psyneuen.2007.01.008
  15. Adam EK, Quinn ME, Tavernier R, McQuillan MT, Dahlke KA, Gilbert KE : Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis. Psychoneuroendocrinology, 83:25-41, 2017.  https://doi.org/10.1016/j.psyneuen.2017.05.018
  16. Katz FH, Shannon IL : Identification and significance of parotid fluid corticosteroids. Acta Endocrinol (Copenh), 46:393-404, 1964.  https://doi.org/10.1530/acta.0.0460393
  17. Kirschbaum C, Pirke KM, Hellhammer DH : The 'Trier Social Stress Test' - a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology, 28:76-81, 1993.  https://doi.org/10.1159/000119004
  18. Seddon JA, Rodriguez VJ, Provencher Y, Raftery-Helmer J, Hersh J, Labelle PR, Thomassin K : Meta-analysis of the effectiveness of the Trier Social Stress Test in eliciting physiological stress responses in children and adolescents. Psychoneuroendocrinology, 116:104582, 2020. 
  19. Dickerson SS, Kemeny ME : Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull, 130:355-391, 2004.  https://doi.org/10.1037/0033-2909.130.3.355
  20. Buske-Kirschbaum A, Jobst S, Wustmans A, Kirschbaum C, Rauh W, Hellhammer D : Attenuated free cortisol response to psychosocial stress in children with atopic dermatitis. Psychosom Med, 59:419-426, 1997.  https://doi.org/10.1097/00006842-199707000-00012
  21. Menet JS, Rosbash M : When brain clocks lose track of time: cause or consequence of neuropsychiatric disorders. Curr Opin Neurobiol, 21:849-857, 2011.  https://doi.org/10.1016/j.conb.2011.06.008
  22. Mahar I, Bambico FR, Mechawar N, Nobrega JN : Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neurosci Biobehav Rev, 38:173-192, 2014.  https://doi.org/10.1016/j.neubiorev.2013.11.009
  23. Law R, Clow A : Stress, the cortisol awakening response and cognitive function. Int Rev Neurobiol, 150:187-217, 2020.  https://doi.org/10.1016/bs.irn.2020.01.001
  24. Ryan MJ, Schloter M, Berg G, Kostic T, Kinkel LL, Eversole K, Macklin JA, Schelkle B, Kazou M, Sarand I, Singh BK, Fischer D, Maguin E, Ferrocino I, Lima N, McClure RS, Charles TC, de Souza RSC, Kiran GS, Krug HL, Taffner J, Roume H, Selvin J, Smith D, Rybakova D, Sessitsch A : Development of Microbiome Biobanks - Challenges and Opportunities. Trends Microbiol, 29:89-92, 2021.  https://doi.org/10.1016/j.tim.2020.06.009
  25. Kilian M, Chapple IL, Hannig M, Marsh PD, Meuric V, Pedersen AM, Tonetti MS, Wade WG, Zaura E : The oral microbiome - an update for oral healthcare professionals. Br Dent J, 221:657-666, 2016.  https://doi.org/10.1038/sj.bdj.2016.865
  26. Fan X, Peters BA, Min D, Ahn J, Hayes RB : Comparison of the oral microbiome in mouthwash and whole saliva samples. PLoS One, 13:E0194729, 2018. 
  27. Cherkasov SV, Popova LY, Vivtanenko TV, Demina RR, Khlopko YA, Balkin AS, Plotnikov AO : Oral microbiomes in children with asthma and dental caries. Oral Dis, 25:898-910, 2019.  https://doi.org/10.1111/odi.13020
  28. Zhang Y, Qi Y, Lo ECM, McGrath C, Mei ML, Dai R : Using next-generation sequencing to detect oral microbiome change following periodontal interventions: A systematic review. Oral Dis, 27:1073-1089, 2021.  https://doi.org/10.1111/odi.13405
  29. Dashper SG, Mitchell HL, Le Cao KA, Carpenter L, Gussy MG, Calache H, Gladman SL, Bulach DM, Hoffmann B, Catmull DV, Pruilh S, Johnson S, Gibbs L, Amezdroz E, Bhatnagar U, Seemann T, Mnatzaganian G, Manton DJ, Reynolds EC : Temporal development of the oral microbiome and prediction of early childhood caries. Sci Rep, 9:19732, 2019. 
  30. Lee E, Park S, Um S, Kim S, Lee J, Jang J, Jeong HO, Shin J, Kang J, Lee S, Jeong T : Microbiome of Saliva and Plaque in Children According to Age and Dental Caries Experience. Diagnostics (Basel), 11:1324, 2021. 
  31. 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 (Maywood), 242:459-472, 2017.  https://doi.org/10.1177/1535370216681550
  32. Kushwaha SS, Multani RK, Kushwaha NS, Gautam S, Jindal DG, Arora KS, Avasthi A : Saliva as a Potential Diagnostic Tool to Evaluate Relationship between Oral Microbiome and Potentially Malignant Disorders for Prevention of Malignant Transformation. Asian Pac J Cancer Prev, 22:125-129, 2021.  https://doi.org/10.31557/APJCP.2021.22.1.125
  33. Farrell JJ, Zhang L, Zhou H, Chia D, Elashoff D, Akin D, Paster BJ, Joshipura K, Wong DT : Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut, 61:582-588, 2012.  https://doi.org/10.1136/gutjnl-2011-300784
  34. Randell RL, Gulati AS, Cook SF, Martin CF, Chen W, Jaeger EL, Schoenborn AA, Basta PV, Dejong H, Luo J, Gallant M, Sandler RS, Long MD, Kappelman MD : Collecting Biospecimens From an Internet-Based Prospective Cohort Study of Inflammatory Bowel Disease (CCFA Partners): A Feasibility Study. JMIR Res Protoc, 5:E3, 2016. 
  35. Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR : A global reference for human genetic variation. Nature, 526:68-74, 2015.  https://doi.org/10.1038/nature15393
  36. Alaeddini R, Walsh SJ, Abbas A : Forensic implications of genetic analyses from degraded DNA - a review. Forensic Sci Int Genet, 4:148-157, 2010.  https://doi.org/10.1016/j.fsigen.2009.09.007
  37. Abraham JE, Maranian MJ, Spiteri I, Russell R, Ingle S, Luccarini C, Earl HM, Pharoah PP, Dunning AM, Caldas C : Saliva samples are a viable alternative to blood samples as a source of DNA for high throughput genotyping. BMC Med Genomics, 5:19, 2012. 
  38. Lorenz TC : Polymerase chain reaction: basic protocol plus troubleshooting and optimization strategies. J Vis Exp, 63:E3998, 2012. 
  39. Sun F, Reichenberger EJ : Saliva as a source of genomic DNA for genetic studies: review of current methods and applications. Oral Health Dent Manag, 13:217-222, 2014. 
  40. Nemoda Z, Horvat-Gordon M, Fortunato CK, Beltzer EK, Scholl JL, Granger DA : Assessing genetic polymorphisms using DNA extracted from cells present in saliva samples. BMC Med Res Methodol, 11:170, 2011. 
  41. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM : Finding the missing heritability of complex diseases. Nature, 461:747-753, 2009.  https://doi.org/10.1038/nature08494
  42. Flanagan JM : Epigenome-wide association studies (EWAS): past, present, and future. Methods Mol Biol, 1238:51-63, 2015.  https://doi.org/10.1007/978-1-4939-1804-1_3
  43. Neri F, Rapelli S, Krepelova A, Incarnato D, Parlato C, Basile G, Maldotti M, Anselmi F, Oliviero S : Intragenic DNA methylation prevents spurious transcription initiation. Nature, 543:72-77, 2017.  https://doi.org/10.1038/nature21373
  44. Lowe R, Gemma C, Beyan H, Hawa MI, Bazeos A, Leslie RD, Montpetit A, Rakyan VK, Ramagopalan SV : Buccals are likely to be a more informative surrogate tissue than blood for epigenome-wide association studies. Epigenetics, 8:445-454, 2013.  https://doi.org/10.4161/epi.24362
  45. Borody TJ, Paramsothy S, Agrawal G : Fecal microbiota transplantation: indications, methods, evidence, and future directions. Curr Gastroenterol Rep, 15:337, 2013. 
  46. Park NJ, Li Y, Yu T, Brinkman BM, Wong DT : Characterization of RNA in saliva. Clin Chem, 52:988-994, 2006.  https://doi.org/10.1373/clinchem.2005.063206
  47. Peakman TC, Elliott P : The UK Biobank sample handling and storage validation studies. Int J Epidemiol, 37(Suppl 1):i2-i6, 2008.  https://doi.org/10.1093/ije/dyn019
  48. Janardhanam SB, Zunt SL, Srinivasan M : Quality assessment of saliva bank samples. Biopreserv Biobank, 10:282-287, 2012.  https://doi.org/10.1089/bio.2011.0039
  49. Al Kuwari H, Al Thani A, Al Marri A, Al Kaabi A, Abderrahim H, Afifi N, Qafoud F, Chan Q, Tzoulaki I, Downey P, Ward H, Murphy N, Riboli E, Elliott P : The Qatar Biobank: background and methods. BMC Public Health, 15:1208, 2015. 
  50. Kim JY, Jeong TS : Saliva: Diagnostic Applications in Medicine and Dentistry. J Korean Acad Pediatr Dent, 42:102-111, 2015.  https://doi.org/10.5933/JKAPD.2015.42.1.102
  51. Thomson WM, Lawrence HP, Broadbent JM, Poulton R : The impact of xerostomia on oral-health-related quality of life among younger adults. Health Qual Life Outcomes, 4:86, 2006. 
  52. Pillemer SR, Matteson EL, Jacobsson LT, Martens PB, Melton LJ 3rd, O'Fallon WM, Fox PC : Incidence of physician-diagnosed primary Sjogren syndrome in residents of Olmsted County, Minnesota. Mayo Clin Proc, 76:593-599, 2001.  https://doi.org/10.1016/S0025-6196(11)62408-7
  53. Tanasiewicz M, Hildebrandt T, Obersztyn I : Xerostomia of Various Etiologies: A Review of the Literature. Adv Clin Exp Med, 25:199-206, 2016.  https://doi.org/10.17219/acem/29375
  54. Valstar MH, de Bakker BS, Steenbakkers R, de Jong KH, Smit LA, Klein Nulent TJW, van Es RJJ, Hofland I, de Keizer B, Jasperse B, Balm AJM, van der Schaaf A, Langendijk JA, Smeele LE, Vogel WV : The tubarial salivary glands: A potential new organ at risk for radiotherapy. Radiother Oncol, 154:292-298, 2021.  https://doi.org/10.1016/j.radonc.2020.09.034
  55. Jellema AP, Slotman BJ, Doornaert P, Leemans CR, Langendijk JA : Impact of radiation-induced xerostomia on quality of life after primary radiotherapy among patients with head and neck cancer. Int J Radiat Oncol Biol Phys, 69:751-760, 2007.  https://doi.org/10.1016/j.ijrobp.2007.04.021
  56. Barbe AG : Medication-Induced Xerostomia and Hyposalivation in the Elderly: Culprits, Complications, and Management. Drugs Aging, 35:877-885, 2018.  https://doi.org/10.1007/s40266-018-0588-5
  57. Langer R, Vacanti JP : Tissue engineering. Science, 260:920-926, 1993.  https://doi.org/10.1126/science.8493529
  58. Yoo C, Vines JB, Alexander G, Murdock K, Hwang P, Jun HW : Adult stem cells and tissue engineering strategies for salivary gland regeneration: a review. Biomater Res, 18:9, 2014. 
  59. Phinney DG, Galipeau J, Krampera M, Martin I, Shi Y, Sensebe L : MSCs: science and trials. Nat Med, 19:812, 2013. 
  60. Kim J, Koo B, Knoblich JA : Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol, 21:571-584, 2020.  https://doi.org/10.1038/s41580-020-0259-3
  61. Maimets M, Rocchi C, Bron R, Pringle S, Kuipers J, Giepmans BN, Vries RG, Clevers H, de Haan G, van Os R, Coppes RP : Long-term in vitro expansion of salivary gland stem cells driven by Wnt Signals. Stem Cell Reports, 6:150-162, 2016.  https://doi.org/10.1016/j.stemcr.2015.11.009
  62. Yoon YJ, Kim D, Tak KY, Hwang S, Kim J, Sim NS, Cho JM, Choi D, Ji Y, Hur JK, Kim H, Park JE, Lim JY : Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands. Nat Commun, 13:3291, 2022. 
  63. Kwon HK, Kim JM, Shin SC, Sung ES, Kim HS, Park GC, Cheon YI, Lee JC, Lee BJ : The mechanism of submandibular gland dysfunction after menopause may be associated with the ferroptosis. Aging (Albany NY), 12:21376-21390, 2020. https://doi.org/10.18632/aging.103882