Natural Antimicrobial Peptides and Their Synthetic Analogues for Effective Oral Microflora Control and Oral Infection Treatment--The Role of Ceragenins in the Development of New Therapeutic Methods  
[PERSON]  
1 Department of Medical Microbiology and Nanob biomedical Engineering, Medical University of Bialystok, 15-222 Bialystok, Poland; [EMAIL_ADDRESS] (M.C. );[EMAIL_ADDRESS] (U.W.) 1 Department of Medical Microbiology and Nanob biomedical Engineering, Medical University of Bialystok, 15-222 Bialystok, Poland; 15-22 Bialystok, Poland;  
and composition [1; 2; 3]. The oral microbiome consists of a diverse range of microorganisms, including bacteria, archaea, fungi, viruses, and protozoa, inhabiting different areas and surfaces in the oral cavity, such as the teeth and soft tissues of the oral mucosa. Furthermore, it is crucial to acknowledge that the oral microbiome can exist in many forms, either as dispersed organisms in saliva or as a biofilm, including plaque, that adheres to oral surfaces. The phylogenetic makeup of microbial communities also undergoes temporal evolution and modifications due to natural and pathological processes [4]. However, it has been proposed that an imbalance in the composition of the oral microbiota may contribute to the occurrence of local and systemic diseases, including squamous cell carcinoma of the head and neck [4], rheumatoid arthritis [5], and hypertension [6]. These observations highlight the importance of understanding and effectively managing oral microbiota, as they reflect the status of the host immunological system and metabolism to a certain degree [7] since oral homeostasis disturbances in bacterial infections depend on several components, which not only include the individual pathogen's characteristics, but also diet and host factors [8]. The subtle balance between commensal and pathogenic oral microorganisms is assured primarily by a spectrum of immune molecules, namely antimicrobial peptides (AMPs)--short (generally \(<100\) amino acids) cationic molecules, which control the oral microbiota's composition quantitatively and qualitatively [9]. AMPs widely exist in nature and have been identified in large numbers in vertebrates, invertebrates, plants, and bacteria [10]. They are an essential component of all living organisms' innate immunity, augmenting the host's physical and chemical barriers, including skin and mucous membranes. Although they are placed into different classes due to amino acid composition, size, and conformational differences (including anionic peptides, linear cationic \(\alpha\)-helical peptides, and cationic peptides enriched for specific amino acids) [11], they display a variety of distinctive and overlapping biological functions, allowing them to modulate the antimicrobial capability of the host via antibacterial, antiparasitic, antifungal, and antiviral activities. In this aspect, cathelicidins, including human cathelicidin LL-37, and defensins are recognized as the most vital contributors to oral hemostasis maintenance [11]. This review focuses on the significance of AMPs for oral health and disease prevention and describes how AMPs contribute to maintaining oral homeostasis by providing an immediate and effective defense against microbial pathogens, modulating immune responses, and preserving the balance of the oral microbiome. The clinical utility of synthetic analogs of AMPs, particularly lipid-based analogs (so-called ceragening, CSAs, i.e., cationic steroid antibiotics), and their potential as therapeutic agents for the prevention and treatment of oral infections and diseases, described in already established and most up-to-date reports, will be given special consideration herein. The increased stability of ceragening, specificity of their activity, decreased likelihood of resistance development, antibiofilm characteristics, and immunomodulatory qualities render them advantageous alternatives to current therapeutic approaches.