Diversity and stability relationships in the murine microbiome

描述(申请人提供)：正如每个人类基因组都是独一无二的，人体内和体内的微生物群落也是独一无二的。这个充满活力的群落--微生物群--通过合成维生素、帮助消化、教育免疫系统和提供对病原体的定植抵抗力来补充人类基因组，以维持健康。尽管人们普遍认为这种微生物群落对维持健康至关重要，而且抗生素或压力对群落的干扰会导致疾病，但人们普遍缺乏对 关于塑造与寄主有关的社区的生态原则和具体机制。为了实现这一目标，关键是要制定一个量化的框架来描述 生物多样性在塑造和维持寄主相关社区稳定方面的作用。这项建议的目的是评估和模拟宿主相关微生物群落中微生物区系的多样性与其稳定性之间的关系。这项拟议研究的中心假设是，肠道微生物群内多样性的增加将导致社区层面的稳定性更大，但种群层面的稳定性更低。这一假说的理论基础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，植物总生物量的变化是减少的，但单个植物种群的生物量的变化并不因多样性而稳定。这一假说将通过产生与老鼠相关的具有不同水平多样性的微生物群落来检验，这些微生物群落将被用于评估肠道群落的变化，并使用16S rRNA和随机测序方法相结合的数学模型。这项研究的具体目标是：1)对“正常”的小鼠相关微生物群落进行建模；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寄主相关微生物群落的动态提供强有力的理论基础。这些创新性的研究将评估在控制遗传、饮食、环境、年龄和性别等因素的情况下，个体小鼠之间的差异水平。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，因为我们将首次能够测量微生物组的组成和功能的正常变化并对其进行建模。此外，拟议研究中所追求的原则和生态模型将影响我们对人类健康和疾病的理解。 公共卫生相关性：已知与人类相关的微生物群落结构和功能的波动会影响健康和疾病。拟议的研究将对公众健康产生重大影响，因为它提供了一个量化框架，可用于预测抗生素和病原体对健康的影响。

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. PUBLIC HEALTH RELEVANCE: Fluctuations in the structure and function of the microbial communities associated with humans are known to affect health and disease. The proposed research will have a significant impact on public health by providing a quantitative framework that can be used to make predictions regarding the effects of antibiotics and pathogens on health.