Antimicrobial Peptides Emerge as Promising Alternative to Antibiotics in Oral Disease Treatment

A recent review published in Translational Dental Research examines the therapeutic potential of antimicrobial peptides (AMPs) for treating 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 naturally occurring molecules could address the growing problem of antibiotic resistance in oral medicine while offering multifunctional benefits beyond traditional antimicrobial approaches.

Traditional treatments for oral diseases like dental caries, periodontitis, and oral cancer primarily rely on antibiotics, but their efficacy has diminished due to widespread bacterial resistance. AMPs represent a promising alternative as key components of the innate immune system that physically destroy microbial cell membranes rather than targeting specific metabolic pathways. This unique mechanism minimizes resistance development while providing additional biological functions including immune regulation, inflammation reduction, and tissue repair promotion with high biocompatibility to human cells.

According to senior author Qiang Feng, AMPs demonstrate significant therapeutic applications across multiple oral conditions. In dental caries treatment, peptides like Temporin-GHa derivatives, ZXR-2, and GH12 inhibit cariogenic bacteria such as Streptococcus mutans, interfere with biofilm formation, and promote 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. Synthetic peptides like Nal-P-113 show similar therapeutic potential.

The review highlights AMP applications in more complex oral conditions as well. In oral cancer therapy, peptides such as Piscidin-1 and LL-37 induce cancer cell death through membrane disruption and apoptotic pathways while modulating anti-tumor immune responses. For fungal infections, AMPs like P-113 and Nisin A demonstrate efficacy against oral candidiasis, while peptides including 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, indicating their clinical translation potential.

Beyond direct therapeutic applications, AMPs show promise in various medical technologies. Researchers are developing them 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. They also function as diagnostic markers for oral diseases by detecting changes in their expression levels, providing a dual-purpose approach to oral healthcare.

Despite their 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 concerns. Large-scale production also presents cost barriers. The review identifies several solutions researchers have developed, 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 implications of this research extend beyond individual patient treatment to broader public health concerns. As antibiotic resistance continues to threaten global health, AMPs offer a sustainable alternative with lower resistance potential. Their multifunctional properties could transform oral disease management from reactive treatment to proactive prevention and regeneration. Future research directions include 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.

The study's findings suggest that AMPs could fundamentally change oral medicine approaches, particularly for conditions where traditional antibiotics have become less effective. As research continues to address translation challenges, these peptides may become standard components in preventive and therapeutic oral healthcare, potentially reducing the global burden of oral diseases that affect billions worldwide. The comprehensive nature of this review provides both researchers and clinicians with valuable insights into current advancements and future directions for AMP implementation in dental practice.