Antimicrobial Peptides Show Promise as Alternative to Antibiotics in Treating Oral Diseases

Antimicrobial peptides (AMPs) represent a promising alternative to traditional antibiotics for treating major oral diseases affecting approximately 3.5 billion people worldwide, including dental caries, periodontitis, and oral cancer. Unlike conventional 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. These small-molecule polypeptides, key components of the innate immune system, also possess multiple biological functions such as regulating immune responses, reducing inflammation, and promoting tissue repair, with high biocompatibility to human cells.

In a new study published in Translational Dental Research, researchers reviewed AMP classification, antimicrobial mechanisms, and roles in treating oral diseases. The research, available at https://doi.org/10.1016/j.tdr.2025.100046, demonstrates that in dental caries treatment, AMPs like Temporin-GHa derivatives, ZXR-2, and GH12 can inhibit the growth of cariogenic bacteria such as Streptococcus mutans, interfere with biofilm formation, and even promote tooth remineralization. For periodontitis, human-derived AMPs and synthetic peptides effectively kill periodontal pathogens, regulate inflammatory responses by inhibiting pro-inflammatory cytokine secretion, and enhance periodontal 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. AMPs have also shown significant efficacy in treating oral candidiasis and alleviating oral mucositis by inhibiting infection and promoting wound healing. Several AMPs have entered clinical trials, including C16G2 for dental caries, Nal-P-113 for periodontitis, and P-113 for oral candidiasis, demonstrating their clinical potential.

Beyond direct therapy, AMPs are being developed into implant coatings to prevent peri-implant infections, oral dressings for sustained release, and combined 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. However, clinical translation faces challenges including stability issues affected by oral enzymes, pH fluctuations, and high salt concentrations; potential cytotoxicity and immunogenicity from cationic and amphiphilic properties; and high production costs.

Researchers have developed strategies to address these challenges, 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. 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 to promote clinical application.