Int J Stomatol ›› 2022, Vol. 49 ›› Issue (2): 212-219.doi: 10.7518/gjkq.2022028

• Reviews • Previous Articles     Next Articles

Research progress of salivary proteins as predictive biomarkers for early childhood caries

Zhu Jinyi(),Fan Qi,Zhou Yuan,Zou Jing,Huang Ruijie()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2021-07-11 Revised:2021-11-20 Online:2022-03-01 Published:2022-03-15
  • Contact: Ruijie Huang;
  • Supported by:
    Science and Technology Project Fund of the Health Planning Committee of Sichuan Province(19PJ074)


The rapid progress of early childhood caries (ECC) and difficulty in early diagnosis have seriously affected the physical and mental health of children. Therefore, early prediction and preventive intervention for children at high risk are effective ways to control the disease. With the development of proteomics technology, salivary proteins are showing strong advantages for disease prediction and early diagnosis. Recent studies have shown that salivary proteins regulate the oral microecological environment through a variety of natural defense mechanisms and play an important role in ECC prevention. Salivary protein levels are associated with the host’s susceptibility to dental caries and are a potential predictor for caries risk. This review summarizes the mechanism of how different salivary proteins, including antimicrobial peptides, glycoproteins, enzymes, and immunoglobulins, influence ECC, as well as the research progress of how salivary proteins are used in disease prediction as biomarkers. On this basis, the application of salivary proteins in ECC risk assessment was prospected.

Key words: early childhood caries, salivary proteins, dental caries susceptibility, biomarkers

CLC Number: 

  • R780.1

[1] Kazeminia M, Abdi A, Shohaimi S, et al. Dental caries in primary and permanent teeth in children’s worldwide, 1995 to 2019: a systematic review and meta-analysis[J]. Head Face Med, 2020, 16(1): 22.
doi: 10.1186/s13005-020-00237-z
[2] American Academy of Pediatric Dentistry. Policy on early childhood caries (ECC): classifications, consequences, and preventive strategies[J]. Pediatr Dent, 2016, 38(6): 52-54.
[3] 卫新. 国家卫生计生委发布全国第四次口腔健康流行病学调查结果[J]. 中国卫生画报, 2017(9): 64.
Wei X. The National Health and Family Planning Commission releases the results of the fourth national oral health epidemiological survey[J]. Chin Health Pictor, 2017(9): 64.
[4] 邹静. 儿童龋病的风险性评估[J]. 华西口腔医学杂志, 2014, 32(1): 1-4.
Zou J. Caries risk assessment in children[J]. West China J Stomatol, 2014, 32(1): 1-4.
[5] Hemadi AS, Huang R, Zhou Y, et al. Salivary proteins and microbiota as biomarkers for early childhood caries risk assessment[J]. Int J Oral Sci, 2017, 9(11): e1.
doi: 10.1038/ijos.2017.35
[6] 邓晓宇, 张蕴涵, 邹静. 低龄儿童龋的早期生物学管理[J]. 国际口腔医学杂志, 2020, 47(5): 581-588.
Deng XY, Zhang YH, Zou J. Early biological management of early childhood caries[J]. Int J Stomatol, 2020, 47(5): 581-588.
[7] Khurshid Z, Naseem M, Sheikh Z, et al. Oral antimicrobial peptides: types and role in the oral cavity[J]. Saudi Pharm J, 2016, 24(5): 515-524.
pmid: 27752223
[8] Steinstraesser L, Kraneburg U, Jacobsen F, et al. Host defense peptides and their antimicrobial-immunomodulatory duality[J]. Immunobiology, 2011, 216(3): 322-333.
doi: 10.1016/j.imbio.2010.07.003 pmid: 20828865
[9] Mai S, Mauger MT, Niu LN, et al. Potential applications of antimicrobial peptides and their mimics in combating caries and pulpal infections[J]. Acta Biomater, 2017, 49: 16-35.
doi: 10.1016/j.actbio.2016.11.026
[10] Jurczak A, Kościelniak D, Papież M, et al. A study on β-defensin-2 and histatin-5 as a diagnostic marker of early childhood caries progression[J]. Biol Res, 2015, 48: 61.
doi: 10.1186/s40659-015-0050-7 pmid: 26520150
[11] Colombo NH, Ribas LF, Pereira JA, et al. Antimicrobial peptides in saliva of children with severe early childhood caries[J]. Arch Oral Biol, 2016, 69: 40-46.
doi: 10.1016/j.archoralbio.2016.05.009
[12] Phattarataratip E, Olson B, Broffitt B, et al. Streptococcus mutans strains recovered from caries-active or caries-free individuals differ in sensitivity to host antimicrobial peptides[J]. Mol Oral Microbiol, 2011, 26(3): 187-199.
doi: 10.1111/j.2041-1014.2011.00607.x pmid: 21545696
[13] Toomarian L, Sattari M, Hashemi N, et al. Comparison of neutrophil apoptosis, α-defensins and calprotectin in children with and without severe early childhood caries[J]. Iran J Immunol, 2011, 8(1): 11-19.
doi: IJIv8i1A2 pmid: 21427491
[14] Lips A, Antunes LS, Antunes LA, et al. Genetic polymorphisms in DEFB1 and miRNA202 are involved in salivary human β-defensin 1 levels and caries experience in children[J]. Caries Res, 2017, 51(3): 209-215.
doi: 10.1159/000458537
[15] Ribeiro TR, Dria KJ, de Carvalho CB, et al. Salivary peptide profile and its association with early childhood caries[J]. Int J Paediatr Dent, 2013, 23(3): 225-234.
[16] Nilsson BO. What can we learn about functional importance of human antimicrobial peptide LL-37 in the oral environment from severe congenital neutropenia (Kostmann disease)[J]. Peptides, 2020, 128: 170311.
doi: 10.1016/j.peptides.2020.170311
[17] Davidopoulou S, Diza E, Menexes G, et al. Salivary concentration of the antimicrobial peptide LL-37 in children[J]. Arch Oral Biol, 2012, 57(7): 865-869.
doi: 10.1016/j.archoralbio.2012.01.008 pmid: 22336091
[18] Wuersching SN, Huth KC, Hickel R, et al. Inhibitory effect of LL-37 and human lactoferricin on growth and biofilm formation of anaerobes associated with oral diseases[J]. Anaerobe, 2021, 67: 102301.
doi: 10.1016/j.anaerobe.2020.102301 pmid: 33249255
[19] Levine M. Susceptibility to dental caries and the salivary proline-rich proteins[J]. Int J Dent, 2011, 2011: 1-13.
[20] Bhalla S, Tandon S, Satyamoorthy K. Salivary proteins and early childhood caries: a gel electrophoretic analysis[J]. Contemp Clin Dent, 2010, 1(1): 17-22.
doi: 10.4103/0976-237X.62515
[21] Fonteles CSR, Guerra MH, Ribeiro TR, et al. Association of free amino acids with caries experience and mutans streptococci levels in whole saliva of children with early childhood caries[J]. Arch Oral Biol, 2009, 54(1): 80-85.
doi: 10.1016/j.archoralbio.2008.07.011
[22] Zakhary GM, Clark RM, Bidichandani SI, et al. Acidic proline-rich protein Db and caries in young children[J]. J Dent Res, 2007, 86(12): 1176-1180.
doi: 10.1177/154405910708601207 pmid: 18037651
[23] Azen EA, Maeda N. Molecular genetics of human salivary proteins and their polymorphisms[J]. Adv Hum Genet, 1988, 17: 141-199.
pmid: 3055850
[24] Strömberg N, Esberg A, Sheng NF, et al. Genetic- and lifestyle-dependent dental caries defined by the acidic proline-rich protein genes PRH1 and PRH2[J]. EBioMedicine, 2017, 26: 38-46.
doi: S2352-3964(17)30462-0 pmid: 29191562
[25] 胡云明, 黄美华. 唾液富组蛋白在口腔疾病中的作用[J]. 国外医学·口腔医学分册, 1995, 22(4): 200-203.
Hu YM, Huang MH. The role of saliva histone-rich protein in oral diseases[J]. Foreign Med Sci(Stomatol), 1995, 22(4): 200-203.
[26] Sun X, Huang X, Tan X, et al. Salivary peptidome profiling for diagnosis of severe early childhood caries[J]. J Transl Med, 2016, 14(1): 240.
doi: 10.1186/s12967-016-0996-4
[27] Ao S, Sun XY, Shi XR, et al. Longitudinal investigation of salivary proteomic profiles in the development of early childhood caries[J]. J Dent, 2017, 61: 21-27.
doi: 10.1016/j.jdent.2017.04.006
[28] Shimotoyodome A, Kobayashi H, Tokimitsu I, et al. Statherin and histatin 1 reduce parotid saliva-promoted Streptococcus mutans strain MT8148 adhesion to hydroxyapatite surfaces[J]. Caries Res, 2006, 40(5): 403-411.
pmid: 16946609
[29] 李远贵, 石四箴. 儿童唾液富酪蛋白与患龋状况的分析研究[J]. 口腔医学研究, 2009, 25(6): 778-780.
Li YG, Shi SZ. Analysis of the salivary statherin in caries-free and caries-susceptible children[J]. J Oral Sci Res, 2009, 25(6): 778-780.
[30] 陈敏, 刘海霞. 高分子量唾液粘蛋白含量与乳牙患龋相关性研究[J]. 中国美容医学, 2014, 23(4): 322-324.
Chen M, Liu HX. High molecular weight salivary mucin content and deciduous teeth caries correlation studies correlation of high-molecular-weight salivary mucin content and primary caries status[J]. Chin J Aesthetic Med, 2014, 23(4): 322-324.
[31] 刘志云, 阙国鹰. 高分子量唾液粘蛋白含量与乳牙患龋相关性的研究[J]. 牙体牙髓牙周病学杂志, 2011, 21(9): 510-513.
Liu ZY, Que GY. Correlation of high-molecular-weight salivary mucin content and primary caries status[J]. Chin J Conserv Dent, 2011, 21(9): 510-513.
[32] 鄢国伟, 黄文明, 薛红蕾, 等. 6~8岁儿童龋病相关唾液蛋白组的电喷雾离子肼—串联质谱分析[J]. 华西口腔医学杂志, 2014, 32(3): 297-302.
Yan GW, Huang WM, Xue HL, et al. Relationship between dental caries and salivary proteome by electrospray ionization ion-trap tandem mass spectrometry in children aged 6 to 8 years[J]. West China J Stomatol, 2014, 32(3): 297-302.
[33] Angwaravong O, Pitiphat W, Bolscher JG, et al. Evaluation of salivary mucins in children with deciduous and mixed dentition: comparative analysis between high and low caries-risk groups[J]. Clin Oral Investig, 2015, 19(8): 1931-1937.
doi: 10.1007/s00784-015-1428-1
[34] Lynge Pedersen AM, Belstrøm D. The role of natural salivary defences in maintaining a healthy oral microbiota[J]. J Dent, 2019, 80(Suppl 1): S3-S12.
doi: 10.1016/j.jdent.2018.08.010
[35] Moslemi M, Sattari M, Kooshki F, et al. Relationship of salivary lactoferrin and lysozyme concentrations with early childhood caries[J]. J Dent Res Dent Clin Dent Prospects, 2015, 9(2): 109-114.
doi: 10.15171/joddd.2015.022
[36] 郝高峰, 林焕彩. 唾液乳铁蛋白和溶菌酶含量与乳牙患龋的关系[J]. 中华口腔医学杂志, 2009, 44(2): 82-84.
Hao GF, Lin HC. Relationship of concentration of lactoferrin and lysozyme in saliva and dental caries in primary dentition[J]. Chin J Stomatol, 2009, 44(2): 82-84.
[37] Rajkumaar J, Mathew MG. Association of severe early childhood caries with salivary ferritin[J]. J Family Med Prim Care, 2020, 9(8): 3991-3993.
doi: 10.4103/jfmpc.jfmpc_9_20
[38] Subramaniam P, Sharma A, Moiden S. Analysis of salivary IgA, amylase, lactoferrin, and lysozyme before and after comprehensive dental treatment in children: a prospective study[J]. Contemp Clin Dent, 2017, 8(4): 526.
doi: 10.4103/ccd.ccd_103_17
[39] Abbasoğlu Z, Tanboğa İ, Calvano Küchler E, et al. Early childhood caries is associated with genetic variants in enamel formation and immune response genes[J]. Caries Res, 2015, 49(1): 70-77.
doi: 10.1159/000362825 pmid: 25531160
[40] Wang MC, Qin M. Lack of association between LTF gene polymorphisms and different caries status in primary dentition[J]. Oral Dis, 2018, 24(8): 1545-1553.
doi: 10.1111/odi.2018.24.issue-8
[41] Wang K, Zhou XD, Li W, et al. Human salivary proteins and their peptidomimetics: values of function, early diagnosis, and therapeutic potential in combating dental caries[J]. Arch Oral Biol, 2019, 99: 31-42.
doi: S0003-9969(18)30664-2 pmid: 30599395
[42] 白洁, 周琼, 包振英, 等. 有龋和无龋儿童四种唾液蛋白成分的比较[J]. 中华口腔医学杂志, 2007, 42(1): 21-23.
Bai J, Zhou Q, Bao ZY, et al. Comparison of salivary proteins between children with early childhood caries and children without caries[J]. Chin J Stomatol, 2007, 42(1): 21-23.
[43] Lertsirivorakul J, Petsongkram B, Chaiyarit P, et al. Salivary lysozyme in relation to dental caries among Thai preschoolers[J]. J Clin Pediatr Dent, 2015, 39(4): 343-347.
doi: 10.17796/1053-4628-39.4.343 pmid: 26161606
[44] Hatipoglu O, Saydam F. Effects of the carbonic anhydrase Ⅵ gene polymorphisms on dental caries: a meta-analysis[J]. Dent Med Probl, 2019, 56(4): 395-400.
doi: 10.17219/dmp/110453
[45] de-Sousa ET, Lima-Holanda AT, Nobre-Dos-santos M. Carbonic anhydrase Ⅵ activity in saliva and biofilm can predict early childhood caries: a preliminary study[J]. Int J Paediatr Dent, 2021, 31(3): 361-371.
doi: 10.1111/ipd.v31.3
[46] 侯雯, 苏达, 阙国鹰. 碳酸酐酶Ⅵ与4~5岁儿童龋病相关性的研究[J]. 口腔医学研究, 2018, 34(4): 363-366.
Hou W, Su D, Que GY. Correlation between carbonic anhydraseⅥ level and dental caries among children aged 4-5 years[J]. J Oral Sci Res, 2018, 34(4): 363-366.
[47] 李静雅, 黄洋. 基质金属蛋白酶在龋病中的研究进展[J]. 口腔医学研究, 2019, 35(12): 1122-1124.
Li JY, Huang Y. Research progress of matrix metalloproteinases in caries[J]. J Oral Sci Res, 2019, 35(12): 1122-1124.
[48] 王潇, 王欣, 秦满. 唾液基质金属蛋白酶2、9与儿童龋病相关性的初步研究[J]. 北京大学学报(医学版), 2018, 50(3): 527-531.
Wang X, Wang X, Qin M. A preliminary study of saliva matrix metalloproteinases (MMP-2 and MMP-9) in children with caries[J]. J Peking Univ (Heal Sci), 2018, 50(3): 527-531.
[49] Marcotte H, Lavoie MC. Oral microbial ecology and the role of salivary immunoglobulin A[J]. Microbiol Mol Biol Rev, 1998, 62(1): 71-109.
doi: 10.1128/MMBR.62.1.71-109.1998
[50] Bagherian A, Jafarzadeh A, Rezaeian M, et al. Comparison of the salivary immunoglobulin concentration levels between children with early childhood caries and caries-free children[J]. Iran J Immunol, 2008, 5(4): 217-221.
doi: IJIv5i4A5 pmid: 19098366
[51] Bagherian A, Asadikaram G, Asadikaram G. Comparison of some salivary characteristics between children with and without early childhood caries[J]. Indian J Dent Res, 2012, 23(5): 628-632.
doi: 10.4103/0970-9290.107380
[52] 翟韶. 解析高龋儿童全唾液免疫生化与龋病相关性的研究[J]. 中国实用医药, 2015, 10(1): 100-101.
Zhai S. Analyze the study of the correlation between whole saliva immunobiochemistry and caries in children with high caries[J]. China Pract Med, 2015, 10(1): 100-101.
[53] 张玉杰, 赵晓军, 赵丽, 等. 318例牙龋病患儿口腔幽门螺旋杆菌感染、唾液口腔pH改变的临床分析[J]. 空军医学杂志, 2017, 33(5): 326-329.
Zhang YJ, Zhao XJ, Zhao L, et al. Clinical analysis of oral Helicobacter pylori infections and changes of oral salivary pH in 318 children with caries[J]. Med J Air Force, 2017, 33(5): 326-329.
[54] 徐月桦, 叶娟, 胡镜清, 等. 唾液免疫球蛋白与疾病[J]. 中国免疫学杂志, 2015, 31(8): 1120-1123.
Xu YH, Ye J, Hu JQ, et al. Saliva immunoglobulin and disease[J]. Chin J Immunol, 2015, 31(8): 1120-1123.
[55] 沈磊. 唾液中SIgA、IgA蛋白酶与儿童龋病关系的研究[D]. 沈阳: 中国医科大学, 2000.
Shen L. Study on the relationship between SIgA and IgA proteases in saliva and childhood caries[D]. Shenyang: China Medical University, 2000.
[56] Smith DJ, King WF, Gilbert JV, et al. Structural integrity of infant salivary immunoglobulin A (IgA) in IgA1 protease-rich environments[J]. Oral Microbiol Immunol, 1998, 13(2): 89-96.
doi: 10.1111/omi.1998.13.issue-2
[57] Yang Y, Li YH, Lin YH, et al. Comparison of immunological and microbiological characteristics in children and the elderly with or without dental caries[J]. Eur J Oral Sci, 2015, 123(2): 80-87.
doi: 10.1111/eos.2015.123.issue-2
[58] Colombo NH, Pereira JA, da Silva ME, et al. Relationship between the IgA antibody response against Streptococcus mutans GbpB and severity of dental caries in childhood[J]. Arch Oral Biol, 2016, 67: 22-27.
doi: 10.1016/j.archoralbio.2016.03.006
[59] Cao XX, Fan J, Chen J, et al. Immunogenicity and prediction of epitopic region of antigen AgⅠ/Ⅱ and glucosyltransferase from Streptococcus mutans[J]. 2016, 36(3): 416-421.
[60] de Farias DG, Bezerra AC. Salivary antibodies, amylase and protein from children with early childhood caries[J]. Clin Oral Investig, 2003, 7(3): 154-157.
doi: 10.1007/s00784-003-0222-7
[61] Pyati SA, Naveen Kumar R, Kumar V, et al. Salivary flow rate, pH, buffering capacity, total protein, oxidative stress and antioxidant capacity in children with and without dental caries[J]. J Clin Pediatr Dent, 2018, 42(6): 445-449.
[62] 王艳, 李存荣, 曾晓莉, 等. 6~7岁无龋与龋活跃儿童唾液糖蛋白水平的比较研究[J]. 上海交通大学学报(医学版), 2016, 36(6): 835-838.
Wang Y, Li CR, Zeng XL, et al. Comparative study on the level of salivary glycoproteins in 6-7 years old caries free and caries active children[J]. J Shanghai Jiaotong Univ (Med Sci), 2016, 36(6): 835-838.
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[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[9] . [J]. Foreign Med Sci: Stomatol, 2004, 31(02): 126 -128 .
[10] . [J]. Inter J Stomatol, 2008, 35(S1): .