In vitro models of subgingival communities and their in vivo pathogenic potential

龈下群落的体外模型及其体内致病潜力

• 批准号: 8623646
• 负责人: Patricia Diaz
• 金额: $ 22.08万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8623646
• 关键词: Affect; Animal Model; Bacteria; Behavior; Biological Preservation; Biomass; Bioreactors; Characteristics; Communities; Complex; Dependency; Development; Disease; Ecology; Environment; Etiology; Event; Forsythia; Functional disorder; Growth; Health; High-Throughput Nucleotide Sequencing; Human; Immune; Immune response; In Vitro; Individual; Inflammation; Inflammatory; Knowledge; Lead; Mediating; Metabolic; Modeling; Monitor; Mucins; Mus; Nature; Nutritional; Oral; Oral cavity; Oxidative Stress; Oxygen; Pathogenesis; Pathogenicity; Periodontal Pocket; Periodontitis; Periodontium; Population; Porphyromonas gingivalis; Prevalence; Preventive; Process; Relative (related person); Research; Ribosomal RNA; Role; Serum; Source; Structure; Taxon; Testing; Therapeutic; Time; Tissues; Treponema denticola; Weight; base; bone loss; improved; in vitro Model; in vivo; member; microbial; microbial community; microbiome; microorganism; named group; novel; novel strategies; pathogen; pressure; prevent; public health relevance; pyrosequencing

Project Summary Periodontitis is an inflammatory condition of the supporting tooth structures that results from the interaction of pathogenic subgingival communities with the host. The pathophysiology of this condition is not completely understood and thus the development of novel preventive or therapeutic strategies remains elusive. Microbial communities are complex dynamic entities in which microorganisms interact with each other, therefore displaying different phenotypic characteristics than individual species. Moreover, a community context modifies the pathogenic potential of microorganisms, which is realized not only by their direct interaction with host tissues but also indirectly by modulating the behavior of the whole community. Therefore, understanding the etiology of periodontitis requires considering microbial communities as the infectious challenge rather than focusing on single species as causative agents. Community models that approximate the taxonomic complexity, environmental conditions and growth rate of microorganisms in the subgingival environment are not available. Such models are necessary to investigate the inter-species interactions that support pathogenic communities. Moreover, animal models of periodontitis are required in which the pathogenic potential of human-like communities could be investigated. In this proposal, we will use recently acquired knowledge on the microbiome composition of humans with periodontitis to develop a 20-species model subgingival community. This model will be developed under continuous culture in nutritional and environmental conditions similar to those in vivo. Using this community model we will investigate inter-species interactions important for the survival of periodontitis-associated species. In particular, we will test the role of a group called "subgingival core species" which are important components of communities in health and disease and potentially serve as community metabolic anchors by supporting periodontitis-associated taxa. We will then evaluate the colonization and pathogenicity of the model 20-species community in the murine oral cavity, testing the hypothesis that microorganisms growing as a community and pre-adapted to environmental pressures such as oxygen are better able to colonize and induce periodontitis than single species. Accordingly, the specific aims of this proposal are: 1) To develop and characterize a chemostat-based subgingival community model representative of periodontitis and test the role of core species as fundamental for the survival of periodontitis- associated community members and 2) To develop a community-based oral gavage murine model of periodontitis. The models proposed will have great impact in the field as they will allow research on the pathogenesis of periodontitis to move beyond the study of single species, thereby facilitating identification of key events that modulate the establishment of pathogenic communities and their effects on host tissues. This knowledge is likely to direct the development of new strategies for preservation of periodontal health.

项目摘要 牙周炎是一种支持牙结构的炎症状态，由牙周炎的相互作用引起。 与宿主共生的致病菌落。这种情况的病理生理学还不完全。 因此，开发新的预防或治疗战略仍然难以捉摸。微生物 群落是微生物相互作用的复杂动态实体，因此 表现出不同于个体物种的表型特征。此外，社区上下文修改 微生物的致病潜力，这不仅通过它们与宿主的直接相互作用来实现 但也间接地通过调节整个社区的行为来实现。因此，理解 牙周炎的病因学要求将微生物群落视为感染挑战，而不是 专注于单一物种作为致病因素。与分类学相近的社区模型 龈下环境中微生物的复杂性、环境条件和生长速度是 不可用。这样的模型对于研究支持致病的物种间相互作用是必要的。 社区。此外，需要牙周炎的动物模型，在这种动物模型中，牙周炎的致病潜力 可以对类似人类的社区进行调查。在这份提案中，我们将使用最近获得的关于 牙周炎患者的菌群组成建立20种菌种模型的研究 社区。这一模式将在营养和环境条件下的连续培养下开发。 与活体中的相似。使用这个群落模型，我们将研究物种间的相互作用，这对于 牙周炎相关物种的生存。特别是，我们将测试一种名为“牙龈下”的组织的作用 核心物种“是健康和疾病方面群落的重要组成部分，并有可能成为 通过支持牙周炎相关的分类群来支持社区新陈代谢锚。然后我们将评估 20种模式菌落在小鼠口腔中的定植和致病性 假设微生物作为一个群落生长并预先适应环境压力，如 氧气比单一菌种更能定植和诱发牙周炎。相应地，具体目标是 这一建议的主要内容是：1)开发和表征基于恒化器的牙龈下群落模型 代表牙周炎，并测试核心物种作为牙周炎生存基础的作用- 相关社区成员和2)开发基于社区的小鼠口腔灌胃模型 牙周炎。提出的模型将在该领域产生重大影响，因为它们将使研究 牙周炎的发病机制超越了单一物种的研究，从而促进了对 调节病原群落的建立及其对宿主组织的影响的关键事件。这 这些知识可能会指导新的策略的发展，以保持牙周健康。