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EN
Saliva represents a highly complex biological environment containing numerous protein and peptides. These factors are responsible for maintaining oral homeostasis and providing protection against microorganisms. The human oral cavity harbors a remarkably diverse microbiome, comprising more than 700 bacterial species as well as numerous viruses and fungi. The microbiological balance of the oral microbiome, essential for maintaining host health, is tightly regulated by proteins, antimicrobial peptides (AMPs), and other bioactive components of saliva. Disruption of this balance can lead to dysbiosis, contributing to the onset of oral and systemic diseases. Antimicrobial peptides are defined as short amino acid sequences that constitute an essential component of innate immunity, capable of directly targeting bacteria, viruses, fungi, and protozoa. In saliva, examples include histatins, defensins, cystatins, and protein fragments, which act as the first line of defense against pathogens through mechanisms such as disruption of microbial membrane integrity, modulation of immune responses, and metal ion chelation. Divalent metal ions, such as Cu(II) and Zn(II), play a particularly important role by contributing to an increased net positive charge, participating in the formation of defined secondary structures in complexes with AMPs, modulating their antimicrobial activity, and shaping a microenvironment that restricts microbial growth. Given the growing threat of antibiotic resistance, salivary antimicrobial peptides represent a promising therapeutic alternative. In recent years, increasing attention has been directed towards structural modifications of these molecules, such as enantiomeric substitution (L → D). It enhances their resistance to enzymatic degradation, prolongs biological activity, and strengthens antimicrobial properties while maintaining the ability to coordinate metal ions. The aim of this review is to highlight the role of salivary antimicrobial peptides in maintaining oral microbial balance, to discuss their mechanisms of action, and to present potential therapeutic opportunities arising from their natural properties and structural modifications.
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