Abstract
Periodontitis is an infectious, inflammatory, non-communicable disease characterized by tissue destruction driven by host responses to dysbiotic shifts in oral microbial communities. The subgingival microbiome constitutes a complex ecosystem in which bacteria, fungi, viruses, and archaea interact via interkingdom communication to modulate the inflammatory response through molecular mechanisms that remain largely unknown. This narrative review aims to understand how functional imbalances within the microbiome alter the microenvironment and promote uncontrolled inflammation responsible for periodontal tissue damage, with implications for systemic disease. The search strategy was conducted according to the PRISM-S extension, to include studies evaluating interkingdom host-pathogen interactions at the gingiva interphase leading to microbial and immune dysbiosis. The discovery of fungi acting as opportunistic pathogens highlights their role in enhancing biofilm virulence and exacerbating host responses, contributing to the total inflammatory burden. Similarly, viruses and archaea influence bacterial metabolism through mechanisms including lysis, nutrient recycling, horizontal gene transfer, and interspecies hydrogen transfer. This interkingdom crosstalk disrupts symbiosis, facilitating enhanced biofilm formation, increased production of virulence factors, and antibiotic resistance. A better understanding of the interkingdom perspective necessitates a comprehensive polymicrobial approach to diagnosis and treatment that extends beyond simply controlling bacteria to include the modulation of interkingdom communication systems. Developing new therapeutic alternatives that address these complex interactions is essential for improving outcomes achieved with mechanical therapy and managing the interrelationships between periodontitis and other systemic diseases.