Insights to Preventive Dentistry via Salivary Defensin Peptide: Evaluating B-Defensins for Caries Control and Periodontal Disease Prevention :A Systematic Review and Meta-Analysis
DOI:
https://doi.org/10.36283/ziun-pjmd14-3/070Keywords:
β-Defensins,, Dental Caries Prevention, Periodontal Disease, Systematic Review, Meta-AnalysisAbstract
Background: Salivary β-defensins form an essential part of oral immune system activity since they lead microbial balance control and help prevent dental caries and periodontal diseases. This systematic review and meta-analysis examine the role of salivary β-defensins in preventive dentistry by evaluating their association with dental caries incidence and their potential contribution to periodontal disease prevention.
Methods: This review was as to the PRISMA 2020 standards. Until April 2025, PubMed, Scopus, Web of Science, and Google Scholar were searched to identify English-language studies that measured the salivary levels of salivary β-defensin or HNP-1 levels in connection to dental caries or periodontal disease. Out of the eight studies that were identified as eligible, there were observational designs and clinical trials. The following instruments were applied to determine the risk of bias: NOS and Cochrane. In RevMan 5.4.1, odds ratio (OR) and standardized mean difference (SMD) pooled estimates and their 95 percent confidence interval (CIs) were calculated using a random-effects model. The I2 statistic was used to determine heterogeneity. Subgroup and sensitivity analysis were described in narrative.
Results: 830 patients were included in 8 studies conducted, evaluating salivary beta-defensins and HNPs with dental caries and periodontal disease. Meta-analysis revealed significantly higher odds of the altered β-defensin levels amongst disease groups than in the controls OR = 1.54; 95% CI: 1.16–2.05; I² = 2.8%). HNPs Pooled analysis also indicated higher odds, although it did not reach significance (OR = 2.38; 95% CI: 0.98, 5.77), whereas levels of hBD-3 did not differ significantly between groups (SMD = - 0.15, 95% CI: -1.341.04, I2 = 94%). Subgroup and sensitivity analyses gave equivalent results in beta-defensins, but said there was diversity in HNP studies. The risk of bias was low to moderate in the majority of the studies.
Discussion: The existing research indicates that β-defensins could serve preventive dentistry in terms of biomarker detection and therapeutic development yet more research standards and patient-specific methods should be operationalized to advance this potential. Researchers need to conduct studies across multiple centers in order to independently demonstrate and apply these findings.
References
1. Diamond G, Ryan L. Beta-defensins: what are they doing in the oral cavity? Oral Dis. 2011 Oct;17(7):628-635. doi:10.1111/j.1601-0825.2011.01799.x.
2. Devine DA, Cosseau C. Host defense peptides in the oral cavity. Adv Appl Microbiol. 2008;63:281-322. doi:10.1016/S0065-2164(07)00008-1.
3. Atalay N, Balci N, Gürsoy M, Gürsoy UK. Systemic factors affecting human beta-defensins in oral cavity. Pathogens. 2024 Aug;13(8):654. doi:10.3390/pathogens13080654.
4. Abiko Y, Nishimura M, Kaku T. Defensins in saliva and the salivary glands. Med Electron Microsc. 2003 Dec;36(4):247-252. doi:10.1007/s00795-003-0225-0.
5. Mathews M, Jia HP, Guthmiller JM, Losh G, Graham S, Johnson GK, et al. Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands. Infect Immun. 1999 Jun;67(6):2740-2745. doi:10.1128/IAI.67.6.2740-2745.1999.
6. Liu Y, Qv W, Ma Y, Zhang Y, Ding C, Chu M, et al. The interplay between oral microbes and immune responses. Front Microbiol. 2022 Nov;13:1009018. doi:10.3389/fmicb.2022.1009018.
7. Khurshid Z, Naseem M, Sheikh Z, Najeeb S, Shahab S, Zafar MS. Oral antimicrobial peptides: Types and role in the oral cavity. Saudi Pharm J. 2016 Sep;24(5):515-524. doi:10.1016/j.jsps.2015.02.015.
8. Wilson SS, Wiens ME, Smith JG. Antiviral mechanisms of human defensins. J Mol Biol. 2013 Dec;425(24):4965-4980. doi:10.1016/j.jmb.2013.09.038.
9. Wei Y, Zheng L, Xie X, Yang X, Liao J. Recent advances in stimuli responsive hydrogels for oral disease treatment. Mater Des. 2024 Apr;240:112817. doi:10.1016/j.matdes.2024.112817.
10. Prasad SV, Fiedoruk K, Daniluk T, Piktel E, Bucki R. Expression and function of host defense peptides at inflammation sites. Int J Mol Sci. 2020 Jan;21(1):104. doi:10.3390/ijms21010104.
11. Lertpimonchai A, Rattanasiri S, Vallibhakara SA, Attia J, Thakkinstian A. The association between oral hygiene and periodontitis: A systematic review and meta-analysis. Int Dent J. 2017 Dec;67(6):332-343. doi:10.1111/idj.12317.
12. Horst JA, Tanzer JM, Milgrom PM. Fluorides and other preventive strategies for tooth decay. Dent Clin North Am. 2018 Apr;62(2):207-234. doi:10.1016/j.cden.2017.11.003.
13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71. doi: 10.1136/bmj.n71.
14. Jha K, Sharma H, Vella V, Mandal NB, Pendyala SK, Khan MM, et al. Role of salivary physicochemical and peptide levels in dental caries among children: An original research. J Pharm Bioallied Sci. 2022 Apr;14(Suppl 1):S292-S294. doi:10.4103/jpbs.jpbs_755_21.
15. Ramezani J, Khaligh MR, Ansari G, Yazdani Y, Mohammadi S. Association of salivary physicochemical characteristics and peptide levels with dental caries in children. J Indian Soc Pedod Prev Dent. 2021 Apr-Jun;39(2):189-195. doi:10.4103/JISPPD.JISPPD_251_20.
16. Sandoval F, Faleiros S, Cabello R, Díaz-Dosque M, Rodríguez G, Escobar A. The consumption of milk supplemented with probiotics decreases the occurrence of caries and the salivary concentration of hβD-3 in children. Clin Oral Investig. 2021 Jun;25(6):3823-3830. doi:10.1007/s00784-020-03712-8.
17. Ozsin-Ozler C, Duruel O, Pinar A, Özbek B, Yaz İ, Ataman-Duruel ET, et al. Dental caries and associated salivary biomarkers in patients with cystic fibrosis. Pediatr Pulmonol. 2022 Nov;57(11):2839-2846. doi:10.1002/ppul.26145.
18. Faheem S, Maqsood S, Hasan A, Imtiaz F, Shaikh F, Farooqui WA, et al. Associations of early childhood caries with salivary beta defensin-3 and childhood anemia: A case-control study. BMC Oral Health. 2021 Sep;21(1):445. doi:10.1186/s12903-021-01810-x.
19. Gürsoy UK, Gürsoy M, Liukkonen A, Suominen AL, Könönen E. Salivary human β-defensin 1-3 and human α-defensin-1 levels in relation to the extent of periodontal disease and tooth loss in the elderly. J Clin Med. 2023 Feb;12(3):976. doi:10.3390/jcm12030976.
20. Öztürk A, Kurt-Bayrakdar S, Avci B. Comparison of gingival crevicular fluid and serum human beta-defensin-2 levels between periodontal health and disease. Oral Dis. 2021 Jul;27(4):993-1000. doi:10.1111/odi.13597.
21. Ansari Moghadam S, Pishadast S, Gholami L, Alijani E, Ansari Moghadam A, Hadilou M, et al. Comparison of salivary beta-defensin-1 levels in patients with periodontitis before and after phase I periodontal therapy. J Adv Periodontol Implant Dent. 2024 Jun;16(1):30-35. doi:10.34172/japid.2024.002.
22. Dale BA, Fredericks LP. Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease. Curr Issues Mol Biol. 2005;7(2):119-133. doi:10.1093/jac/dki103.
23. Abiko Y, Saitoh M. Salivary defensins and their importance in oral health and disease. Curr Pharm Des. 2007;13(30):3065-3072. doi:10.2174/138161207782110417.
24. Izadi N, Keikha M, Ghazvini K, Karbalaei M. Oral antimicrobial peptides and new therapeutic strategies for plaque-mediated diseases. Gene Rep. 2020;21:100811. doi:10.1016/j.genrep.2020.100811.
25. Ślebioda Z, Szponar E, Kowalska A. Defensins and their role in the maintenance of the oral cavity homeostasis – a literature review. Cent Eur J Immunol. 2013;38(1):111-117. doi:10.5114/ceji.2013.34367.
26. Jayakaran TG, Rekha CV, Annamalai S, Baghkomeh PN. Salivary peptide human neutrophil defensin1–3 and its relationship with early childhood caries. Dent Res J. 2020 Nov-Dec;17(6):459-464. doi:10.4103/1735-3327.302480.
27. Tao R, Jurevic RJ, Coulton KK, Tsutsui MT, Roberts MC, Kimball JR, et al. Salivary antimicrobial peptide expression and dental caries experience in children. Antimicrob Agents Chemother. 2005 Sep;49(9):3883-3888. doi:10.1128/AAC.49.9.3883-3888.2005.
28. Kareem SJ, Al-Ghurabi BH. Regulatory role of human neutrophil peptides (HNP1-3) on interleukin-6 production in early childhood caries. J Emerg Med Trauma Acute Care. 2023;2023(3):11. doi:10.5339/jemtac.2023.midc.11.
29. Zhang J, Liu Z, Zhou Z, Huang Z, Yang Y, Wu J, et al. HNP-1: From structure to application thanks to multifaceted functions. Microorganisms. 2025 Feb;13(2):458. doi:10.3390/microorganisms13020458.
30. Barrera J, Tortolero S, Rivas A, Flores C, Gonzales E. Increased expression and levels of human β defensins (hBD2 and hBD4) in adults with dental caries. J Health Sci. 2013 Jun;3(2):70. doi:10.17532/jhsci.2013.70.
31. Greer A, Zenobia C, Darveau RP. Defensins and LL-37: A review of function in the gingival epithelium. Periodontol 2000. 2013 Oct;63(1):67-79. doi:10.1111/prd.12028.
32. Bedi T, Mahendra J, Ambalavanan N. Defensins in periodontal health. Indian J Dent Res. 2015 Jul-Aug;26(4):340-346. doi:10.4103/0970-9290.167627.
33. Navarra CO, Robino A, Pirastu N, Bevilacqua L, Gasparini P, Di Lenarda R, et al. Caries and innate immunity: DEFB1 gene polymorphisms and caries susceptibility in genetic isolates from North-Eastern Italy. Caries Res. 2016;50(6):589-594. doi:10.1159/000450965.
34. Hatipoğlu Ö, Saydam F. Association between rs11362 polymorphism in the beta-defensin 1 (DEFB1) gene and dental caries: A meta-analysis. J Oral Biosci. 2020 Sep;62(3):272-279. doi:10.1016/j.job.2020.06.004.
35. Wu L, Li Z, Zhou J, Ma B, Yu F, Zheng X, et al. An association analysis for genetic factors for dental caries susceptibility in a cohort of Chinese children. Oral Dis. 2022 Mar;28(2):480-494. doi:10.1111/odi.13758.
36. Mazziotta C, Tognon M, Martini F, Torreggiani E, Rotondo JC. Probiotics mechanism of action on immune cells and beneficial effects on human health. Cells. 2023 Jan;12(1):184. doi:10.3390/cells12010184.
37. Petrariu OA, Barbu IC, Niculescu AG, Constantin M, Grigore GA, Cristian RE, et al. Role of probiotics in managing various human diseases, from oral pathology to cancer and gastrointestinal diseases. Front Microbiol. 2024 Jan;14:1296447. doi:10.3389/fmicb.2023.1296447.
38. Sedghi L, DiMassa V, Harrington A, Lynch SV, Kapila YL. The oral microbiome: Role of key organisms and complex networks in oral health and disease. Periodontol 2000. 2021 Oct;87(1):107-131. doi:10.1111/prd.12393.
39. Gm A. Oral biofilm and its impact on oral health, psychological and social interaction. J Dent Health Oral Disord Ther. [n.d.];12(1):1-5. doi:10.23937/2469-5734/1510127.
40. Negrini TC, Carlos IZ, Duque C, Caiaffa KS, Arthur RA. Interplay among the oral microbiome, oral cavity conditions, the host immune response, diabetes mellitus, and its associated-risk factors—An overview. Front Oral Health. 2021;2:697428. doi:10.3389/froh.2021.697428.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Pakistan Journal of Medicine and Dentistry
This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an open-access article distributed under the terms of the CreativeCommons Attribution License (CC BY) 4.0 https://creativecommons.org/licenses/by/4.0/
Metrics
How to Cite
