Arginine metabolism in periodontal health and diseases

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ABSTRACT Periodontitis is one of the most common infectious diseases affecting humans worldwide, and this oral disease has been linked to systemic diseases. Current knowledge points to a dysbiosis in periodontitis or loss of the balance between the microbial consortia and the host immune and inflammatory responses, which results in destruction of periodontal tissues. An expanding area of research focus on therapeutic interventions that modulate microbial ecology to restore homeostasis of human biofilms, and thus health. Robust evidence supports a significant role of arginine metabolism in the ecological balance of supragingival biofilms and inhibition of dental caries. Arginine metabolism via the arginine deiminase pathway (ADS) produces ammonia, which counteracts the effects of biofilm acidification from bacterial glycolysis. Our clinical studies revealed a positive correlation between caries activity and low arginolytic capacity of the supragingival biofilms. Interestingly, recent in vivo and vitro studies revealed a potential multifaceted role of arginine in the ecology of subgingival biofilms. It has also been shown that arginine-sensing pathways are activated by microbial interactions common to subgingival communities, and that arginine may affect the virulence of certain periodontal pathogens. However, the arginolytic potential of oral samples from individuals with different periodontal health-status remains unexplored. The main goal of this application is to begin to explore the relationship between ADS activity in subgingival biofilms and periodontal health-status of adults over time. This proposal seeks to address the paucity of knowledge on whether arginine metabolism via ADS by the subgingival microbiome is positively or negatively associated with periodontal health in a comprehensive and clinically relevant fashion. To accomplish this goal, Aim 1 will evaluate the relationships between: a) arginine metabolism via ADS by subgingival plaque, b) plaque levels of arginine and certain arginine metabolites (i.e. citrulline, ornithine, agmatine and putrescine), and c) periodontal health-status of adults over a period of 12 months. Aim 2 will correlate plaque ADS activity and levels of arginine and arginine metabolites with local levels of gingival crevicular fluid (GCF) immuno-inflammatory biomarkers. Collectively, these studies will advance our understanding of how arginine metabolism in subgingival biofilms influences the disease process of periodontitis and how the arginolytic potential of subgingival biofilms correlates with the dynamic processes of immune responses in periodontal health and disease over time. This research will have a direct translational application by providing the scientific basis for the rational design of new arginine-based risk assessment tools and approaches that can be widely distributed to at-risk populations for disease prevention and control.