Identification of bacterial strains for development of an oral probiotic aimed at increasing nitric oxide bioavailability

一氧化氮(No)在调节生理的多种细胞和分子机制中起着重要作用。 以及各种器官和系统的功能。NO的枯竭及其生物可利用性的降低导致了 几种人类疾病的病理学，包括贫血、疟疾、心力衰竭、肥胖、糖尿病和 神经退行性变。最近的研究表明，口腔微生物区系通过调节NO的作用来调节NO的稳态。 一些有能力将营养阴离子硝酸盐还原为亚硝酸盐和NO的细菌。几个 临床试验已经利用了这个硝酸盐-亚硝酸盐-NO循环，通过口服硝酸盐来传递NO。 然而，许多人对口服硝酸盐没有反应，我们推测这是由于缺乏 硝酸盐转化为亚硝酸盐的细菌。因此，开发像益生菌这样的微生物组调节剂来增强 和/或执行增加的硝酸盐还原并且NO形成可以潜在地用作恢复的解决方案 降低了NO水平和生物利用度。该项目的目标是测试口腔细菌在 确定口服硝酸盐转化为血浆亚硝酸盐的程度，同时开发新的人类来源 硝酸盐-亚硝酸盐-NO形成能力的益生菌及其定植和形成的黏附能力测定 上皮细胞中的生物膜。在目标1中，我们将使用新的、高通量的筛选分析来确定候选人 从口腔中获得的高效转化硝酸盐为亚硝酸盐的细菌及其特性 这些菌株。在目标2中，我们将确定硝酸盐转化为亚硝酸盐的口腔定植能力。 细菌菌株。在目标3中，我们将测试这些细菌菌株在确定 在小鼠模型中将口服硝酸盐转化为血浆亚硝酸盐。成功完成这些研究可以 导致益生菌对人类引起的疾病没有动态平衡的破坏。

Nitric oxide (NO) plays critical roles in a myriad of cellular and molecular mechanisms regulating physiology and function of various organs and systems. Depletion of NO and its reduced bioavailability contributes to the pathology of several human diseases including anemia, malaria, heart failure, obesity, diabetes and neurodegeneration. Recent reports suggest that oral microbiota regulate NO homeostasis through the action of some bacteria that have the ability to perform reduction of the nutrient anion nitrate to nitrite and NO. Several clinical trials have taken advantage of this nitrate-nitrite-NO cycle employing oral nitrate to deliver NO. However, many individuals do not respond to oral nitrate, and we hypothesize that this is due to a deficiency in nitrate to nitrite converting bacteria. Hence, developing microbiome modulators like probiotics to enhance and/or perform increased nitrate reduction and NO formation can potentially serve as a solution to recover diminished NO levels and bioavailability. The goal of this project is to test the role of oral bacteria in determining the extent of conversion of oral nitrate to plasma nitrite while developing novel human-origin probiotics of nitrate-nitrite-NO formation abilities and determine their adherence potential to colonize and form biofilms in epithelia. In Aim 1 we will use novel, high throughput screening assays to identify candidate bacterial strains with efficient nitrate to nitrite conversion abilities obtained from the oral cavity and characterize these strains. In Aim 2 we will determine the oral cavity colonizing capabilities of the nitrate to nitrite converting bacterial strains. In Aim 3, we will test the role of these bacterial strains’ in determining the extent of conversion of oral nitrate to plasma nitrite in a murine model. Successful completion of these studies could lead to probiotics against human diseases caused by NO homeostasis abrogation.