Antimicrobial Peptides Emerge as Promising Alternative for Global Oral Disease Treatment

A new review published in Translational Dental Research examines the potential of antimicrobial peptides as alternative treatments for major oral diseases affecting approximately 3.5 billion people worldwide. The study, available at https://doi.org/10.1016/j.tdr.2025.100046, analyzes how these small-molecule polypeptides could address the growing problem of antibiotic resistance while offering multifunctional therapeutic benefits. Unlike traditional antibiotics that target specific metabolic pathways, AMPs primarily act by physically destroying microbial cell membranes—a mechanism that minimizes the risk of inducing bacterial resistance. Senior author Qiang Feng explains that AMPs also possess multiple biological functions including regulating immune responses, reducing inflammation, and promoting tissue repair, with high biocompatibility to human cells.

The research details specific applications for various oral conditions. In dental caries treatment, AMPs like Temporin-GHa derivatives, ZXR-2, and GH12 can inhibit the growth of cariogenic bacteria such as Streptococcus mutans and interfere with biofilm formation. For periodontitis, human-derived AMPs and synthetic peptides effectively kill periodontal pathogens while regulating inflammatory responses and enhancing tissue regeneration. In oral cancer therapy, AMPs such as Piscidin-1 and LL-37 induce cancer cell death through membrane disruption and apoptotic pathways while modulating anti-tumor immune responses. The review also notes that AMPs like P-113 and Nisin A show significant efficacy against oral candidiasis, while peptides such as IB-367 and Histatin-5 alleviate oral mucositis by inhibiting infection and promoting wound healing.

Several AMPs have already entered clinical trials, including C16G2 for dental caries, Nal-P-113 for periodontitis, and P-113 for oral candidiasis. Beyond direct therapy, researchers are developing AMPs into implant coatings to prevent peri-implant infections, oral dressings for sustained release, and combination therapies with antibiotics or nanoparticles to enhance therapeutic effects. They also show promise as diagnostic markers for oral diseases by detecting changes in their expression levels. Despite this potential, clinical translation faces significant challenges. Oral enzymes, pH fluctuations, and high salt concentrations affect AMP stability, while their cationic and amphiphilic properties may lead to cytotoxicity and immunogenicity. Large-scale production also remains costly.

To address these issues, researchers have developed strategies including chemical modification, 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 future research should focus on clarifying AMP interaction mechanisms with oral microbiota and host cells, accelerating peptide screening through artificial intelligence, and developing tailored formulations for the oral microenvironment. As antibiotic resistance continues to undermine traditional treatments, AMPs' multifunctional properties and low resistance potential position them as potentially transformative agents in oral medicine.