Elucidating the Role of the Intestinal Microbiota in Pathogen Resistance

阐明肠道微生物群在病原体抵抗中的作用

• 批准号: 8026703
• 负责人: ROBERT A BRITTON
• 金额: $ 44.18万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8026703
• 关键词: Address; Affect; Antibiotics; Area; Autoimmune Diseases; Bacteria; Bioavailable; Biology; Bioreactors; Characteristics; Chronic; Clostridium difficile; Communicable Diseases; Communities; Complex; Development; Diarrhea; Disease; Elements; Enteral; Epithelium; Foundations; Genetic; Genotype; Germ-Free; Gnotobiotic; Goals; Health; Human; Human Microbiome; Immune response; Immune system; In Vitro; Individual; Infection; Inflammatory Bowel Diseases; Instruction; Intestines; Invaded; Investigation; Knowledge; Lipids; Mus; Nature; Nosocomial Infections; Nutrient; Obesity; Organ; Organism; Outcome; Physiological; Predisposition; Probiotics; Process; Resistance; Role; Screening procedure; Solid; Study models; Technology; Tissue Harvesting; Work; enteric pathogen; gastrointestinal; improved; in vivo; interest; microbial; microbial community; microbiome; microorganism; mouse model; novel; nutrition; pathogen; research study; response; therapeutic target

PROJECT SUMMARY (See instructions): The bacteria that reside within and upon us have a key role in maintaining our health. The intestinal microbiota provides a number of important functions for the host including processing and acquisition of nutrients, development of the immune system, modulation of bioavailable lipids, and serves as a barrier against pathogens. How the microbiota carries out these functions and how they can be manipulated in a diseased state to restore health is pooriy understood. The vast complexity of the gut microbial community has only recently begun to be addressed with the emergence of high-throughput sequencing technologies. However, most of the initial studies of the human microbiota have focused on identifying which organisms are present and not on functional aspects of microbial communities. In this project we will address a function of microbial communities of fundamental importance to the host: the ability to keep pathogens from colonizing and/or causing disease. Using bioreactor models and mice with a humanized intestinal microbiota we will begin to uncover the underiying ecological principles of how pathogen resistance is maintained within a community. We will also attempt to understand what types of disruption are sufficient to allow pathogens to invade the community and cause disease. To achieve these goals the following specific aims are proposed; Specific Aim 1. Investigate how microbial community diversity affects the ability of diarrheal pathogens to become established within the community. Specific Aim 2. Assess the effects of microbial community alterations on the ability of pathogens to cause disease in mice carrying a humanized micriobiota. The work proposed in these specific aims will address a key function of the intestinal microbiota using a combination of in vitro and in vivo approaches.

项目总结(见说明)： 存在于我们体内和身上的细菌在维持我们的健康方面起着关键作用。肠道 微生物区系为寄主提供了许多重要的功能，包括处理和获取营养物质，发展免疫系统，调节生物可利用的脂质，并作为抵御病原体的屏障。微生物区系如何执行这些功能，以及如何在患病状态下操纵它们以恢复健康，目前还知之甚少。直到最近，随着高通量测序技术的出现，肠道微生物群落的巨大复杂性才开始得到解决。然而，大多数关于人类微生物区系的初步研究都集中在确定存在哪些微生物上，而不是微生物群落的功能方面。在这个项目中，我们将讨论对宿主至关重要的微生物群落的一项功能：防止病原体定植和/或引起疾病的能力。利用生物反应器模型和具有人源化肠道微生物区系的小鼠，我们将开始揭示一个群落中如何维持病原体抗性的潜在生态学原理。我们还将尝试了解哪些类型的破坏足以允许病原体入侵社区并导致疾病。为实现这些目标，具体目标如下 提出；具体目标1.调查微生物群落多样性如何影响腹泻的能力 病原体在社区内形成。具体目标2.评估微生物群落改变对携带人源化微生物群的小鼠致病能力的影响。在这些具体目标中提出的工作将使用体外和体内相结合的方法解决肠道微生物区系的一个关键功能。