Probiotics that moderate pH and antagonize pathogens to promote oral health

益生菌可调节 pH 值并对抗病原体，促进口腔健康

• 批准号: 9234521
• 负责人: Robert A Burne
• 金额: $ 61.5万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9234521
• 关键词: Address; Amino Acids; Animal Model; Animals; Antibiotics; Arginine; Arginine deiminase; Bacteria; Behavior; Biochemical; Biological; Biological Markers; Biological Models; Clinical; Clinical Research; Communicable Diseases; Coupled; Dental; Dental Plaque; Dental caries; Development; Diagnosis; Disease; Enzymes; Formulation; Foundations; Future; Gene Expression Profile; Genetic; Genetic Markers; Genomics; Goals; Growth; Health; Heterogeneity; Human; Human Microbiome; Hydrogen Peroxide; In Vitro; Individual; Light; Metabolic; Metabolic Pathway; Metabolism; Metagenomics; Methodology; Microbial Biofilms; Modeling; Molecular; Monitor; Mouth Diseases; Mycoses; Oral cavity; Oral health; Organism; Outcome; Oxidases; Peptide Hydrolases; Periodontal Diseases; Periodontitis; Phenotype; Probiotics; Property; Research; Risk Assessment; Rodent Model; Role; Running; Science; Solid; Source; Streptococcus; Streptococcus mutans; Structure; Symbiosis; System; Testing; Tissues; Work; bacteriocin; base; biomarker identification; commensal microbes; comparative genomics; design; efficacy evaluation; functional genomics; in vivo; killings; microbial; microbiota; microorganism; mouse model; novel; novel marker; novel therapeutics; oral bacteria; oral biofilm; oral infection; oral microbiome; oral pathogen; pH Homeostasis; pathogen; prebiotics; prevent; probiotic therapy; public health relevance; sound; tool; weapons

 DESCRIPTION (provided by applicant): Numerous in vitro and in vivo studies have shown there are bacteria that may promote oral health. Many of these bacteria have the ability to use the amino acid arginine to raise dental plaque pH, thus inhibiting the formation of cavities. Additionally, many of these potentially beneficial bacteria are able to interfere with the growth o oral pathogens, like Streptococcus mutans, and to block the ability of S. mutans to produce antibiotics that kill beneficial organisms. Thus, identifying isolates of these bacteria with poten beneficial properties and understanding how they modulate disease development would be tremendously valuable in controlling oral infectious diseases, like dental caries and periodontitis The work proposed here is built on the foundation that individual isolates display a profound spectrum of anti-cariogenic properties: in their capacity to utilize arginine via the arginine deiminase system; in their capacity to exert strong antagonistic effects on the growth of oral pathogens; and in their abilities to interfere with the deployment of antagonistic molecules by oral pathogens. When implemented, the study will yield a much-needed, thorough understanding of the genomic structure and associated phenotypic behaviors of a group of abundant commensal streptococci, along with the mechanisms by which these organisms exert probiotic effects in in vitro, in an animal model, and in the human oral cavity. To accomplish these goals, Aim 1 conducts a comparative and functional genomic analysis of a discrete group of low-passage, clinical isolates to characterize the mechanisms for their enhanced capacity to moderate pH through arginine metabolism, to dissect the diverse repertoire of strategies they employ to antagonize oral pathogens, to understand the genetic basis for the ability of these isolates to resist antagonistic molecules deployed by oral pathogens, and to identify genetic markers associated with isolates that have particularly beneficial properties. In Aim 2, we will establish a mouse model of dental caries that is suitable for evaluating the capacity of, and the mechanisms by which, selected isolates from Aim 1 are able to inhibit establishment, persistence, and the initiation and progression of dental caries by S. mutans. Aim 3 will contrast gene expression patterns in isolated human dental plaque from caries-active and caries-free subjects to understand how arginine metabolic pathways and the weapons of commensals and pathogens are deployed in health and disease, as well as to identify novel genetic biomarkers for health and disease. Collectively, the study will provide a comprehensive understanding of mechanisms of pro- and pre-biotic for control of dental caries and guide the development of effective probiotics and symbiotic, while providing the added benefit of enhancing the quality of oral health risk assessments.

 描述(申请人提供)：大量的体外和体内研究表明，有可能促进口腔健康的细菌。这些细菌中的许多都有能力利用氨基酸精氨酸来提高牙菌斑的pH值，从而抑制龋齿的形成。此外，这些潜在有益细菌中的许多都能够干扰口腔病原体的生长，如变形链球菌，并阻止变形链球菌产生杀死有益微生物的抗生素的能力。因此，识别具有潜在有益特性的这些细菌的菌株并了解它们如何调节疾病的发展将在控制口腔感染性疾病(如龋齿和牙周炎)方面具有巨大的价值。这里提出的工作是建立在单个菌株表现出深刻的抗龋性的基础上的：它们通过精氨酸脱亚胺酶系统利用精氨酸的能力；它们对口腔病原体的生长产生强烈的拮抗作用的能力；以及它们干扰口腔病原体部署拮抗分子的能力。实施后，这项研究将产生急需的、彻底的理解一组丰富的共生链球菌的基因组结构和相关的表型行为，以及这些生物在体外、动物模型和人类口腔中发挥益生菌作用的机制。为了实现这些目标，Aim 1对一组低传代的临床分离株进行了比较和功能基因组分析，以表征它们通过精氨酸代谢增强调节pH的能力的机制，剖析它们用来对抗口腔病原体的各种策略，了解这些分离物抵抗口腔病原体所部署的拮抗分子的能力的遗传基础，并确定与具有特别有益特性的分离物相关的遗传标记。在目标2中，我们将建立一种适合于评估从目标1中选择的菌株能够抑制变形链球菌的龋病建立、持续以及发生和发展的能力和机制的龋齿小鼠模型。目的3将比较有龋齿和无龋者牙菌斑的基因表达模式，以了解精氨酸代谢途径以及共生菌和病原体的武器是如何在健康和疾病中部署的，以及寻找新的健康和疾病的遗传生物标记物。总体而言，这项研究将全面了解益生菌和益生菌控制龋齿的机制，并指导开发有效的益生菌和共生菌，同时提供提高口腔健康风险评估质量的额外好处。