Salivary Histatin-5 Depletion and hBD-2 Elevation Consistently Linked to Severe Dental Caries and ECC
Background
Severe dental caries, particularly Early Childhood Caries (ECC), remains a significant global public health challenge, often leading to pain, infection, and impaired quality of life. Current diagnostic and preventive strategies primarily focus on diet and oral hygiene, but host factors like salivary antimicrobial peptides (AMPs) play a crucial role in innate oral immunity. Understanding the specific AMPs associated with caries severity could identify novel biomarkers for disease susceptibility and progression, offering a more personalized approach to prevention and early intervention.
Study Design
This systematic review and meta-analysis synthesized evidence on salivary AMP concentrations in caries-affected versus caries-free individuals, focusing on ECC. A comprehensive search of PubMed, Scopus, and ClinicalKey was conducted up to 2025. Studies reporting salivary concentrations of histatin-5 (HST-5), human β-defensin-1 (hBD-1), β-defensin-2 (hBD-2), β-defensin-3 (hBD-3), human neutrophil peptides 1-3 (HNP1-3), LL-37, and calprotectin were included. Risk of bias was assessed using ROBINS-I, and certainty of evidence with GRADE. Random-effects meta-analyses calculated standardized mean differences (SMDs) and correlation coefficients.
Results
Twelve studies were selected for analysis. Salivary histatin-5 (HST-5) was consistently depleted in severe caries (SMD -20.63; p<0.01) and severe ECC compared to milder disease (SMD -18.19; p<0.01). Conversely, human β-defensin-2 (hBD-2) was significantly higher in children with ECC versus caries-free controls (SMD 1.65; p=0.01), with moderate-certainty evidence. Human neutrophil peptides (HNP1-3) were lower in severe ECC compared to mild disease (SMD -0.63; p=0.03), though with lower certainty.
Histatin-5 depletion and hBD-2 elevation show consistent associations with caries severity, indicating their potential as biomarkers. Human β-defensin-1 (SMD -2.87; p=0.13) and Human β-defensin-3 (SMD -0.16; p=0.47) showed inconsistent or insignificant associations. LL-37 (SMD -0.60; p=0.08) and calprotectin (effect size 0.986; p=0.812) associations were of low certainty.
Key Findings
- Salivary histatin-5 was consistently depleted in severe dental caries (SMD -20.63; p<0.01).
- Histatin-5 was also depleted in severe Early Childhood Caries (ECC) (SMD -18.19; p<0.01).
- Human β-defensin-2 (hBD-2) was significantly elevated in ECC children vs. controls (SMD 1.65; p=0.01).
- Human neutrophil peptides 1-3 (HNP1-3) were lower in severe ECC vs. mild disease (SMD -0.63; p=0.03).
- Associations for hBD-1, hBD-3, LL-37, and calprotectin were inconsistent or of low certainty.
Why It Matters
Identifying specific salivary AMPs like histatin-5 and hBD-2 as reliable biomarkers could revolutionize early detection and risk assessment for dental caries and ECC. This offers a non-invasive method beyond visual inspection or traditional risk factors, potentially allowing for targeted preventive interventions before irreversible damage occurs. Developing salivary diagnostic tests based on these AMPs could enable clinicians to identify high-risk individuals, particularly children, for personalized preventive strategies. While further validation is needed, this research lays the groundwork for future clinical tools that could improve oral health outcomes by leveraging the innate immune response.