ALTERNATIVE THERAPIES TO BACTERIAL INFECTIONS OF THE ORAL CAVITY: A REVIEW
DOI:
https://doi.org/10.33003/fjs-2026-1007-4595Keywords:
Antimicrobial, Antimicrobial resistance, Nanoparticle-based, Oral infection, Phage Therapy.Abstract
Oral infections are among the most prevalent global health conditions and are intrinsically linked to dysbiosis of the oral microbiome and biofilm ecology. In health, a balanced microbial community supports mucosal integrity and immune homeostasis. However, shifts driven by dietary sugars, poor oral hygiene, smoking, systemic disease, and antibiotic exposure promote pathogenic polymicrobial biofilms implicated in dental caries, periodontitis, peri-implantitis, and endodontic infections. These biofilm-mediated diseases, commonly involving Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans, are not only locally destructive but are increasingly associated with systemic conditions including cardiovascular disease, diabetes, rheumatoid arthritis, Alzheimer’s disease, and infective endocarditis. Antimicrobial resistance (AMR) further complicates management, with global mortality exceeding one million deaths annually and a substantial proportion of dental antibiotic prescriptions deemed unnecessary. Conventional therapies such as mechanical debridement combined with antiseptics and systemic antibiotics, provide short-term microbial reduction but are limited by incomplete biofilm penetration, disruption of commensal microbiota, adverse effects, and accelerating resistance. Emerging strategies such as bacteriophage therapy, nanoparticle-based antimicrobials, photodynamic and photothermal therapies, and antimicrobial peptides offer targeted, biofilm-disruptive, and resistance-sparing alternatives. These approaches demonstrate promising antimicrobial efficacy while aiming to preserve microbial balance. However, challenges, including toxicity concerns, regulatory barriers, cost, and limited long-term clinical evidence, remain. Advancing precision antimicrobial interventions may redefine oral infection management by shifting from broad elimination to ecological modulation and targeted biofilm control.
References
Ahmadi, H., Ebrahimi, A., & Ahmadi, F. (2021). Antibiotic Therapy in Dentistry. International Journal of Dentistry, 2021, 1–10. https://doi.org/10.1155/2021/6667624
Ahmed, S. A., Baris, E., Go, D. S., Lofgren, H., Osorio-Rodarte, I., & Thierfelder, K. (2017). Assessing the global economic and poverty effects of antimicrobial resistance. World Bank Policy Research Working Paper, (8133).
Ahn, K. B., Kim, A. R., Kum, K. Y., Yun, C. H., & Han, S. H. (2017). The synthetic human beta-defensin-3 C15 peptide exhibits antimicrobial activity against Streptococcus mutans, both alone and in combination with dental disinfectants. Journal of Microbiology, 55(10), 830-836.
Allaker, R., & Douglas, C. (2015). Non-conventional therapeutics for oral infections. Virulence, 6, 196 - 207. https://doi.org/10.4161/21505594.2014.983783.
Balhaddad, A. A., Kansara, A. A., Hidan, D., Weir, M. D., Xu, H. H. K., & Melo, M. A. S. (2019). Toward dental caries: Exploring nanoparticle-based platforms and calcium phosphate compounds for dental restorative materials. Bioactive Materials, 4, 43–55. https://doi.org/10.1016/j.bioactmat.2018.12.002
Bedran, T. B. L., Mayer, M. P. A., Spolidorio, D. P., & Grenier, D. (2014). Synergistic anti-inflammatory activity of the antimicrobial peptides’ human beta-defensin-3 (hBD-3) and cathelicidin (LL-37) in a three-dimensional co-culture model of gingival epithelial cells and fibroblasts. PLoS One, 9(9), e106766.
Cheraghiyan, M. (2025). Nanotechnology in Dentistry: Potential Applications and Future Perspectives.
Diamond, G., & Ryan, L. K. (2011). Beta‐defensins: what are they REALLY doing in the oral cavity. Oral Diseases, 17(7), 628-635.
Fu, Y., Cannon, R. D., Li, K. C., Ekambaram, M., Cooper, P. R., & Mei, M. L. (2025). Development and characterisation of a novel antimicrobial peptide GA-C16G2 targeting Streptococcus mutans. Journal of Dentistry, 161, 105927. https://doi.org/10.1016/j.jdent.2025.105927
Gajić, I., Tomić, N., Luković, B., Jovićević, M., Kekić, D., Petrovic, M., Janković, M., Trudic, A., Ćulafić, D., Milenković, M., & Opavski, N. (2025). A Comprehensive Overview of Antibacterial Agents for Combating Multidrug-Resistant Bacteria: The Current Landscape, Development, Future Opportunities, and Challenges. Antibiotics, 14. https://doi.org/10.3390/antibiotics14030221.
Gholami, L., Shahabi, S., Jazaeri, M., Hadilou, M., & Fekrazad, R. (2023). Clinical applications of antimicrobial photodynamic therapy in dentistry. Frontiers in Microbiology, 13. https://doi.org/10.3389/fmicb.2022.1020995.
Haque, M., Yerex, K., Kelekis-Cholakis, A., & Duan, K. (2022). Advances in novel therapeutic approaches for periodontal diseases. BMC Oral Health, 22. https://doi.org/10.1186/s12903-022-02530-6.
Huang, S., Qi, M., & Chen, Y. (2023). Photonics-based treatments: Mechanisms and applications in oral infectious diseases. Frontiers in Microbiology, 14. https://doi.org/10.3389/fmicb.2023.948092.
Hwang, G., Liu, Y., & Korostoff, J. (2025). Novel Approaches for Treatment of Intraoral Microbial Infections. Journal of Dental Research, 104, 584 - 593. https://doi.org/10.1177/00220345251317494.
Jao, Y., Ding, S., & Chen, C. (2023). Antimicrobial photodynamic therapy for the treatment of oral infections: A systematic review. Journal of Dental Sciences, 18, 1453 - 1466. https://doi.org/10.1016/j.jds.2023.07.002.
Jiang, Y., Yin, C., Mo, J., Wang, X., Wang, T., Li, G., & Zhou, Q. (2023). Recent progress in carbon dots for anti-pathogen applications in oral cavity. Frontiers in Cellular and Infection Microbiology, 13. https://doi.org/10.3389/fcimb.2023.1251309.
Jiao, Y., Tay, F., Niu, L., & Chen, J. (2019). Advancing antimicrobial strategies for managing oral biofilm infections. International Journal of Oral Science, 11. https://doi.org/10.1038/s41368-019-0062-1.
Kabwe, M., Tucci, J., Darby, I., & Dashper, S. (2025). Oral bacteriophages and their potential as adjunctive treatments for periodontitis: a narrative review. Journal of Oral Microbiology, 17. https://doi.org/10.1080/20002297.2025.2469890.
Łasica, A., Golec, P., Laskus, A., Zalewska, M., Gędaj, M., & Popowska, M. (2024). Periodontitis: etiology, conventional treatments, and emerging bacteriophage and predatory bacteria therapies. Frontiers in Microbiology, 15. https://doi.org/10.3389/fmicb.2024.1469414.
Li, X., Liu, Y., Yang, X., Li, C., & Song, Z. (2022). The Oral Microbiota: Community Composition, Influencing Factors, Pathogenesis, and Interventions. Frontiers in Microbiology, 13. https://doi.org/10.3389/fmicb.2022.895537.
Mahlapuu, M., Håkansson, J., Ringstad, L., & Björn, C. (2016). Antimicrobial peptides: an emerging category of therapeutic agents. Frontiers in cellular and infection microbiology, 6, 194.
Mallineni, S. K., Sakhamuri, S., Kotha, S. L., AlAsmari, A. R. G. M., AlJefri, G. H., Almotawah, F. N., ... & Sajja, R. (2023). Silver nanoparticles in dental applications: A descriptive review. Bioengineering, 10(3), 327.
Mdarhri, H., Benmessaoud, R., Yacoubi, H., Seffar, L., Assimi, H., Hamam, M., Boussettine, R., Filali-Ansari, N., Lahlou, F., Diawara, I., Ennaji, M., & Kettani-Halabi, M. (2022). Alternatives Therapeutic Approaches to Conventional Antibiotics: Advantages, Limitations and Potential Application in Medicine. Antibiotics, 11. https://doi.org/10.3390/antibiotics11121826.
Milho, C., Silva, J., Guimarães, R., Ferreira, I. C. F. R., Barros, L. & Alves, M. J. (2021). Antimicrobials from Medicinal Plants: An Emergent Strategy to Control Oral Biofilms. Applied Sciences, 11(9), 4020. https://doi.org/10.3390/app11094020
Niu, M., Lee, J. J., Hwang, G., Chung, C. H., Wolff, M. S., Zheng, Z., & Li, C. (2025). Usage of Silver Nanoparticles in Orthodontic Appliances. Materials, 19(1), 115.
Peng, X., Cheng, L., You, Y., Tang, C., Ren, B., Li, Y., Xu, X., & Zhou, X. (2022). Oral microbiota in human systematic diseases. International Journal of Oral Science, 14. https://doi.org/10.1038/s41368-022-00163-7.
Radaic, A., & Kapila, Y. (2021). The oralome and its dysbiosis: New insights into oral microbiome-host interactions. Computational and Structural Biotechnology Journal, 19, 1335 - 1360. https://doi.org/10.1016/j.csbj.2021.02.010.
Salehi, B., Kręgiel, D., Mahady, G., Sharifi‐Rad, J., Martins, N., & Rodrigues, C. (2020). Management of Streptococcus mutans-Candida spp. Oral Biofilms’ Infections: Paving the Way for Effective Clinical Interventions. Journal of Clinical Medicine, 9. https://doi.org/10.3390/jcm9020517.
Săndulescu, O., Preoțescu, L., Streinu-Cercel, A., Şahin, G. & Săndulescu, M. (2024). Antibiotic Prescribing in Dental Medicine—Best Practices for Successful Implementation. Tropical Medicine and Infectious Disease, 9(2), 31. https://doi.org/10.3390/tropicalmed9020031
Sedghi, L., Dimassa, V., Harrington, A., Lynch, S., & Kapila, Y. (2021). The oral microbiome: Role of key organisms and complex networks in oral health and disease. Periodontology 2000, 87, 107 - 131. https://doi.org/10.1111/prd.12393.
Silvestre, A., Di Filippo, L., Besegato, J., De Annunzio, S., De Camargo, B., De Melo, P., Rastelli, A., Fontana, C., & Chorilli, M. (2020). Current applications of drug delivery nanosystems associated with antimicrobial photodynamic therapy for oral infections.. International Journal of Pharmaceutics, 120078 . https://doi.org/10.1016/j.ijpharm.2020.120078.
Strandberg, E., Bentz, D., Wadhwani, P., & Ulrich, A. S. (2020). Chiral supramolecular architecture of stable transmembrane pores formed by an α-helical antibiotic peptide in the presence of lyso-lipids. Scientific Reports, 10(1), 4710.
Sudhakara, P., Gupta, A., Bhardwaj, A., & Wilson, A. (2018). Oral Dysbiotic Communities and Their Implications in Systemic Diseases. Dentistry Journal, 6. https://doi.org/10.3390/dj6020010.
Sun, Z., Ma, L., Sun, X., Sloan, A. J., O’Brien‐Simpson, N. M., & Li, W. (2023). The overview of antimicrobial peptide‐coated implants against oral bacterial infections. Aggregate, 4(3), e309. https://doi.org/10.1002/agt2.309
Talapko, J., Meštrović, T., Juzbašić, M., Tomas, M., Erić, S., Horvat Aleksijević, L., Bekić, S., Schwarz, D., Matić, S., Neuberg, M., & Škrlec, I. (2022). Antimicrobial Peptides—Mechanisms of Action, Antimicrobial Effects and Clinical Applications. Antibiotics, 11(10), 1417. https://doi.org/10.3390/antibiotics11101417
Tinoco, J. M., Buttaro, B., Zhang, H., Liss, N., Sassone, L., & Stevens, R. (2016). Effect of a genetically engineered bacteriophage on Enterococcus faecalis biofilms. Archives of oral biology, 71, 80-86.
Theuretzbacher, U., & Piddock, L. (2019). Non-traditional Antibacterial Therapeutic Options and Challenges.. Cell host & microbe, 26 1, 61-72 . https://doi.org/10.1016/j.chom.2019.06.004.
World Health Organization. (2025). Global Antibiotic Resistance Surveillance Report 2025: WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS).
Yang, D., Xiang, Y., Song, F., Li, H., & Ji, X. (2024). Phage therapy: A renewed approach against oral diseases caused by Enterococcus faecalis infections.. Microbial pathogenesis, 106574 . https://doi.org/10.1016/j.micpath.2024.106574.
Yarahmadi, A., Najafiyan, H., Yousefi, M., Khosravi, E., Shabani, E., Afkhami, H., & Aghaei, S. (2025). Beyond antibiotics: exploring multifaceted approaches to combat bacterial resistance in the modern era: a comprehensive review. Frontiers in Cellular and Infection Microbiology, 15. https://doi.org/10.3389/fcimb.2025.1493915.
Yılmaz, D., Güncü, G. N., Könönen, E., Barış, E., Çağlayan, F., & Gursoy, U. K. (2015). Overexpressions of hBD-2, hBD-3, and hCAP18/LL-37 in gingiva of diabetics with periodontitis. Immunobiology, 220(11), 1219-1226.
1Yin, I. X., Udduttulla, A., Xu, V. W., Chen, K. J., Zhang, M. Y., & Chu, C. H. (2025). Use of Antimicrobial Nanoparticles for the Management of Dental Diseases. Nanomaterials, 15(3), 209. https://doi.org/10.3390/nano15030209
2Yin, L., Chino, T., Horst, O. V., Hacker, B. M., Clark, E. A., Dale, B. A., & Chung, W. O. (2010). Differential and coordinated expression of defensins and cytokines by gingival epithelial cells and dendritic cells in response to oral bacteria. BMC immunology, 11(1), 37.
Zhang, Q. Y., Yan, Z. B., Meng, Y. M., Hong, X. Y., Shao, G., Ma, J. J., ... & Fu, C. Y. (2021). Antimicrobial peptides: mechanism of action, activity and clinical potential. Military Medical Research, 8(1), 48.
Zhu, M., Hao, C., Zou, T., Jiang, S., & Wu, B. (2025). Phage therapy as an alternative strategy for oral bacterial infections: a systematic review. BMC Oral Health, 25. https://doi.org/10.1186/s12903-024-05399-9.
Downloads
Published
Issue
Section
Categories
License
Copyright (c) 2026 Samuel Amodu, Ayotundun Christianah Ojelabi, Tochukwu Favour Udochukwu

This work is licensed under a Creative Commons Attribution 4.0 International License.