Arginine metabolism in periodontal health and diseases

摘要 牙周炎是世界范围内影响人类的最常见的传染病之一， 与系统性疾病有关。目前的知识点牙周炎的生态失调或丧失的， 微生物聚生体与宿主免疫和炎症反应之间的平衡，这导致 破坏牙周组织。一个不断扩大的研究领域集中在治疗干预， 调节微生物生态以恢复人体生物膜的动态平衡，从而恢复健康。有力的证据 支持精氨酸代谢在龈上生物膜的生态平衡中的重要作用， 抑制龋齿。通过精氨酸脱亚胺酶途径（ADS）的精氨酸代谢产生氨， 其抵消了来自细菌糖酵解的生物膜酸化的影响。我们的临床研究显示， 龋病活动性与龈上生物膜的低溶解能力呈正相关。 有趣的是，最近的体内和体外研究揭示了精氨酸在微生态学中的潜在多方面作用。 龈下生物膜还已经表明，烟碱敏感途径被微生物激活， 相互作用常见的龈下社区，精氨酸可能会影响某些毒力 牙周病原体然而，来自不同个体的口腔样本的溶解潜力 牙周健康状况仍然未被探索。此应用程序的主要目标是开始探索 成年人龈下生物膜中ADS活性与牙周健康状况的关系这 该提案旨在解决缺乏关于精氨酸代谢是否通过ADS的知识， 龈下微生物组与牙周健康正相关或负相关， 临床相关的时尚。为了实现这一目标，目标1将评估以下之间的关系： B）精氨酸和某些精氨酸代谢物（即，精氨酸和精氨酸代谢物）的菌斑水平。 瓜氨酸、鸟氨酸、胍丁胺和腐胺），以及c）12年期间成人牙周健康状况 个月目的2将斑块ADS活性和精氨酸及精氨酸代谢物水平与局部 龈沟液（GCF）免疫炎症生物标志物的水平。这些研究将 推进我们对龈下生物膜中精氨酸代谢如何影响疾病进程的理解 以及龈下生物膜的溶解潜力与动态过程的关系 牙周健康和疾病的免疫反应。这项研究将有直接的转化 通过为合理设计新的基于药物的风险评估工具提供科学依据， 以及可以广泛分发给高危人群的方法，以预防和控制疾病。

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.