Diversity and stability relationships in the murine microbiome

描述（由申请人提供）：正如每个人类基因组都是独特的一样，居住在人体内和人体上的微生物群体也是如此。这个动态的社区-微生物组-补充了人类基因组，通过合成维生素，协助消化，教育免疫系统和提供对病原体的殖民抵抗力来维持健康。尽管人们普遍认为，这种微生物群落对维持健康至关重要，并且通过抗生素或压力引起的对群落的干扰可以促进疾病，但人们普遍缺乏对微生物群落的了解。 关于生态原则和具体机制，形成主机相关的社区。为了实现这一目标，关键是要制定一个定量框架， 生物多样性在形成和维持与宿主相关的社区的稳定方面的作用。该提案的目的是评估和模拟宿主相关微生物群落中微生物群多样性及其稳定性之间的关系。这项研究的核心假设是，肠道微生物组内的多样性增加将导致更大的社区水平稳定性，但群体水平稳定性降低。这一假说的基本原理来自景观生态学领域的观察，即在高度多样性的生态系统中，植物总生物量生产的变化减少，但单个植物种群生物量的变化并不因多样性而稳定。将通过生成具有不同多样性水平的小鼠相关微生物群落来测试这一假设，这些微生物群落将用于使用16 S rRNA和随机测序方法的组合来评估肠道群落的变化并对其进行数学建模。拟议研究的具体目标是：1）模拟“正常”小鼠相关微生物群落; 2）测量分类多样性对稳定性的影响; 3）评估功能多样性对稳定性的影响。生态学和数学工具的结合将为理解宿主相关微生物群落的动态提供强有力的理论基础。这些创新研究将评估个体小鼠之间的变异水平，其中遗传，饮食，环境，年龄和性别等因素受到控制。拟议的研究将对我们对宿主相关微生物群落的理解产生重大影响，因为这是第一次，我们将能够测量和模拟微生物组组成和功能的正常变化。此外，在拟议的研究中追求的原则和生态建模将影响我们对人类健康和疾病的理解。

DESCRIPTION (provided by applicant): Just as every human genome is unique, so too is the community of microbial populations that reside within and on the human body. This dynamic community - the microbiome - complements the human genome to maintain health by synthesizing vitamins, assisting in digestion, educating the immune system, and providing colonization resistance to pathogens. Although it is widely accepted that this microbial community is critical to maintaining health and that disturbances to the community induced through antibiotics or stress can facilitate disease, there is a general lack of understanding with regards to the ecological principles and specific mechanisms that shape host-associated communities. Toward this goal it is critical to develop a quantitative framework for describing the role of biodiversity in shaping and maintaining the stability of host-associated communities. The objective of this proposal is to evaluate and model the relationships between the diversity of the microbiota and its stability in host-associated microbial communities. The central hypothesis for the proposed research is that increased diversity within the gut microbiome will result in greater community-level stability, but less population-level stability. The rationale for this hypothesis comes from observations in the field of landscape ecology that variation in total plant biomass production is reduced in high diversity ecosystems, but the variation in biomass of individual plant populations is not stabilized by diversity. This hypothesis will be tested by generating mouse-associated microbial communities with varying levels of diversity that will be used to assess and mathematically model changes in the gut community using a combination of 16S rRNA and random sequencing approaches. The specific aims of the proposed research are to 1) model the "normal" mouse-associated microbial community; 2) measure the effects of taxonomic diversity on stability; and 3) assess the effects of functional diversity on stability. Te combination of ecological and mathematical tools will provide a strong theoretical basis to understand the dynamics of host-associated microbial communities. These innovative studies will assess the level of variation between individual mice where factors such as genetics, diet, environment, age, and sex are controlled. The proposed research will have a significant impact on our understanding of host-associated microbial communities because for the first time, we will be able to measure and model the normal variation in the composition and function of the microbiome. Furthermore, the principles and ecological modeling that is pursued in the proposed research will impact our understanding of health and disease in humans.