A new review published in Translational Dental Research examines the potential of antimicrobial peptides (AMPs) as transformative treatments for oral diseases affecting approximately 3.5 billion people worldwide. The research, available at https://doi.org/10.1016/j.tdr.2025.100046, details how these small-molecule polypeptides offer broad-spectrum antimicrobial activity with low propensity to induce bacterial resistance, addressing critical limitations of traditional antibiotic therapies.
Unlike conventional antibiotics that target specific metabolic pathways, AMPs primarily act by physically destroying microbial cell membranes through unique mechanisms that minimize resistance development. Senior author Qiang Feng explains that AMPs demonstrate multifunctional properties including immunomodulation and tissue regeneration promotion, with specific applications across major oral conditions. In dental caries treatment, peptides like Temporin-GHa derivatives, ZXR-2, and GH12 inhibit cariogenic bacteria such as Streptococcus mutans while promoting tooth remineralization.
For periodontitis, human-derived AMPs including α-defensins and β-defensins effectively kill periodontal pathogens while regulating inflammatory responses and enhancing tissue regeneration. The therapeutic potential extends to oral cancer, where peptides such as Piscidin-1 and LL-37 induce cancer cell death through membrane disruption and apoptotic pathways while modulating anti-tumor immune responses. Additional applications show efficacy against oral candidiasis with peptides like P-113 and Nisin A, and oral mucositis treatment with IB-367 and Histatin-5 promoting wound healing.
Several AMPs have progressed to clinical trials, including C16G2 for dental caries, Nal-P-113 for periodontitis, and P-113 for oral candidiasis, demonstrating tangible clinical potential. Beyond direct therapeutic applications, researchers are developing AMPs into implant coatings to prevent peri-implant infections, creating oral dressings for sustained release, and combining them with antibiotics or nanoparticles to enhance therapeutic effects. The peptides also show promise as diagnostic markers for oral diseases through detection of expression level changes.
Despite this potential, clinical translation faces significant challenges including stability issues affected by oral enzymes, pH fluctuations, and high salt concentrations. Cationic and amphiphilic properties may lead to cytotoxicity and immunogenicity concerns, while large-scale production remains costly. Researchers have developed strategies to address these limitations, including chemical modification through N-acetylation and lipidation, nanocarrier delivery systems, sequence optimization with D-amino acids, and microbial or plant-based heterologous expression to improve stability, reduce toxicity, and lower production costs.
The authors emphasize that AMPs' multifunctional properties and low resistance potential position them as transformative agents in oral medicine. Future research should focus on clarifying interaction mechanisms with oral microbiota and host cells, accelerating peptide screening through artificial intelligence, and developing tailored formulations for the oral microenvironment to advance clinical applications. This comprehensive approach addresses the urgent need for safe and effective alternatives to traditional antibiotics amid growing bacterial resistance concerns.
