Diversity and stability relationships in the murine microbiome

小鼠微生物组的多样性和稳定性关系

• 批准号: 8415881
• 负责人: Patrick David Schloss
• 金额: $ 33.6万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8415881
• 关键词: Accounting; Affect; Age; Antibiotics; Behavior; Biodiversity; Bioinformatics; Biological Models; Biomass; Cell Count; Cells; Collaborations; Communities; Complement; Complex; Diabetes Mellitus; Diet; Digestion; Discipline; Disease; Ecology; Ecosystem; Environment; Funding Opportunities; Genes; Genetic; Genomics; Goals; Health; Human; Human Genome; Human Microbiome; Human body; Immune system; Individual; Intestines; Lead; Link; Malignant Neoplasms; Measures; Microbe; Microbiology; Modeling; Mus; Obesity; Opportunistic Infections; Pathogenesis; Periodontal Diseases; Plague; Plants; Population; Process; Production; Protein Family; Public Health; Research; Resistance; Resources; Ribosomal RNA; Role; Scientist; Shapes; Stress; Structure; System; Systems Biology; Technology; Testing; Therapeutic; Time; Variant; Vitamins; Work; base; innovation; interest; microbial; microbial community; microbial genome; microbiome; next generation sequencing; pathogen; prevent; sex; theories; tool; translational medicine

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.

描述（由申请人提供）：就像每个人类基因组都是独特的一样，居住在人体和人体内部和人体的微生物种群社区也是如此。这个动态的社区 - 微生物组 - 通过合成维生素，有助于消化，教育免疫系统并为病原体提供抗性抗性，以补充人类基因组来维持健康。尽管人们普遍认为，这个微生物群落对于维持健康至关重要，并且通过抗生素或压力引起的社区的干扰可以促进疾病，但对 关于塑造与宿主相关的社区的生态原理和特定机制。为了实现这一目标，建立一个定量框架以描述该目标至关重要 生物多样性在塑造和维持与宿主相关社区的稳定性中的作用。该建议的目的是评估和建模微生物群多样性与宿主相关微生物群落中的稳定性之间的关系。拟议的研究的中心假设是，肠道微生物组内的多样性增加将导致社区层面的稳定性更高，但人口水平的稳定性较小。该假设的基本原理来自景观生态学领域的观察结果，即高多样性生态系统中植物生物量的总生物量的变化减少，但是单个植物种群的生物量的变化并未因多样性而稳定。该假设将通过生成具有不同多样性水平的小鼠相关的微生物群落来检验，这些微生物群落将使用16S rRNA和随机测序方法的组合来评估和数学对肠道群落的变化进行建模。拟议研究的具体目的是1）建模“正常”与小鼠相关的微生物群落建模； 2）衡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。生态和数学工具的结合将提供强大的理论基础，以了解与宿主相关的微生物群落的动态。这些创新的研究将评估单个小鼠之间的变异水平，在控制遗传学，饮食，环境，年龄和性别等因素。拟议的研究将对我们对与宿主相关的微生物群落的理解产生重大影响，因为这是我们第一次能够测量和建模微生物组组成和功能的正常变化。此外，拟议的研究中追求的原理和生态建模将影响我们对人类健康和疾病的理解。