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，而这种口腔疾病 与系统性疾病有关。目前的知识表明牙周炎存在生物失调或牙周组织缺失。 微生物联合体与宿主免疫和炎症反应之间的平衡，从而导致 破坏牙周组织。不断扩大的研究领域侧重于治疗干预措施 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 支持精氨酸代谢在牙龈上生物膜生态平衡中的重要作用 抑制龋齿。精氨酸代谢通过精氨酸脱亚胺酶途径(ADS)产生氨， 它抵消了细菌糖酵解引起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低的精氨酸分解能力呈正相关。 有趣的是，最近的体内和体外研究表明，精氨酸在人体内的生态中具有潜在的多方面作用。 龈下生物膜。也有研究表明，精氨酸敏感通路是由微生物激活的。 精氨酸可能会影响某些细菌的毒力 牙周病原体。然而，不同个体的口腔样本的精氨酸分解潜力 牙周健康状况仍未得到研究。这个应用程序的主要目标是开始探索 龈下生物膜中ADS活性与成人牙周健康状况的关系。这 一项提案旨在解决人们对精氨酸代谢是否通过广告的缺乏这一问题 龈下微生物群与牙周健康呈正相关或负相关 与临床相关的时尚。为了实现这一目标，目标1将评估：a)精氨酸之间的关系 B)牙菌斑的精氨酸和某些精氨酸代谢物的水平(即 瓜氨酸、鸟氨酸、胍丁胺和腐胺)，以及c)成年人的牙周健康状况 月份。目标2将斑块ADS活性、精氨酸和精氨酸代谢物水平与局部 牙周沟液(GCF)免疫炎症生物标志物的水平。总的来说，这些研究将 加深对龈下生物膜中精氨酸代谢如何影响疾病进程的理解 以及龈下生物膜的精氨酸分解潜力如何与牙周炎的动态过程相关 随着时间的推移，牙周健康和疾病中的免疫反应。这项研究将有直接的翻译 为基于精氨酸的新型风险评估工具的合理设计提供科学依据 以及可广泛分发给高危人群用于疾病预防和控制的方法。

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.