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 牙周炎是辅助牙齿结构的炎症状况，这是由于相互作用而引起的 与宿主的致病性次命社区。这种疾病的病理生理并不完全 理解，因此新型预防或治疗策略的发展仍然难以捉摸。微生物 社区是微生物相互作用的复杂动态实体，因此 与单个物种显示不同的表型特征。而且，社区环境正在修改 微生物的致病潜力不仅是通过与宿主直接相互作用实现的 组织，也可以间接通过调节整个社区的行为。因此，了解 牙周炎的病因需要将微生物群落视为传染性挑战，而不是 专注于单一物种作为致病剂。近似分类学的社区模型 在次命环境中微生物的复杂性，环境条件和增长率是 无法使用。这样的模型对于研究支持致病性的种间相互作用是必要的 社区。此外，需要牙周炎的动物模型，其中 可以调查类似人类的社区。在此提案中，我们将使用最近获得的知识 人类与牙周炎的微生物组组成，以开发20种多种模型尺寸 社区。该模型将在营养和环境条件下连续文化下开发 类似于体内。使用这种社区模型，我们将研究对种间之间的互动 牙周炎相关物种的存活。特别是，我们将测试一个称为“ subgingival的小组”的作用 核心物种“是健康和疾病社区的重要组成部分，并有可能用作 通过支持牙周炎相关类群，社区代谢锚。然后我们将评估 鼠口腔中20种物种社区的殖民和致病性，测试 假设微生物作为一个社区而生长并预先适应环境压力，例如 氧气比单个物种更好地能够定植和诱导牙周炎。因此，具体目的 该提议的内容是：1）开发和表征基于化学稳定的副群社区模型 牙周炎的代表并检验核心物种作为牙周炎生存至关重要的作用 相关的社区成员和2）开发基于社区的口服口服鼠模型 牙周炎。提出的模型将在该领域产生重大影响，因为它们将允许对 牙周炎的发病机制超出了单一物种的研究，从而促进了 调节病原体群落及其对宿主组织的影响的关键事件。这 知识可能会指导发展牙周健康的新策略。