Determinants of Microbiome Stability Following Pathogen Infection

项目总结-病原体感染后微生物组稳定性的决定因素 人体微生物群(即体内和体内的微生物群落)影响人类健康。 和发展。微生物组组成(存在的微生物种类)和多样性(数量 物种)会影响微生物群的功能。抗生素、饮食变化、环境等干扰 压力或病原体感染会引起微生物群的变化(扰动)，这可能会影响 微生物组功能与人类健康。干扰对微生物群和人类健康的影响可能 微生物组的稳定性，这是微生物组保持稳定结构(多样性)的能力 和组成)和功能，尽管有骚乱。了解控制微生物群稳定性的因素 因此对人类健康很重要。传染病和温度应激是两种扰动 由于反复发生的疾病暴发和人类引起的气候变化，对人类健康的关注日益增加。这个 拟议研究的长期目标是了解气候和疾病如何影响微生物群和 是什么因素控制着微生物群对这些干扰的抵抗力和韧性。具体目标是：(1) 确定病原体感染期间微生物组的多样性和组成如何影响微生物组的稳定性； 以确定长期的温度变化如何影响微生物组对病原体感染的反应。这个 该项目将利用模式生物黑腹果蝇的易驯养性和与人类的相关性 健康和野生果蝇物种的多样性和生态现实主义。具体目标1，夏威夷人 果蝇物种自然具有不同的微生物群，将被用来识别 微生物组结构(多样性和组成)和在细菌病原体感染期间的稳定性。下一首, 将通过操纵微生物组来测试微生物组结构和稳定性之间的因果关系 并将果蝇暴露在病原体下。特定目标2将使用单一种群 在不同的温度下自然进化的果蝇物种，以测试是否适应 温度影响微生物群和宿主对病原体感染的反应。在这两个具体目标中， 微生物组结构将通过微生物系统发育标记(16S，ITS)的DNA测序来测量， 它们确定了存在的微生物分类群及其相对丰度。将对微生物组功能进行评估 使用基于基因预测功能能力的鸟枪式元基因组学和转录组学 直读法。病原菌诱导的微生物群扰动将被测量为变化(前后 感染)对微生物组结构和功能的影响。稳定性是扰动的反面，也就是避免 尽管有骚乱，但还是要改变。微生物组结构对稳定性的影响将通过测试如何确定 感染前的微生物群落结构影响感染后的扰动程度。这个项目将 产生关于微生物组结构-稳定性关系的知识，这将为未来奠定基础 研究了解稳定性和复原力的潜在机制以及对宿主健康的影响。

PROJECT SUMMARY - Determinants of Microbiome Stability Following Pathogen Infection The human microbiome (i.e., the consortium of microbes that reside in and on the body) affects human health and development. Microbiome composition (the microbial species that are present) and diversity (the number of species) can affect microbiome function. Disturbances such as antibiotics, dietary shifts, environmental stress or pathogen infection can cause changes (perturbations) in the microbiome, which can affect microbiome function and human health. The impacts of disturbances on the microbiome and human health can be mitigated by microbiome stability, which is the microbiome’s capacity to maintain stable structure (diversity and composition) and function despite disturbances. Understanding the factors that control microbiome stability is therefore important for human health. Infectious disease and temperature stress are two disturbances of growing concern to human health due to recurring disease outbreaks and human-induced climate change. The long-term goal of the proposed research is to understand how climate and disease affect the microbiome and what factors control microbiome resistance and resilience to these disturbances. The specific aims are: (1) to determine how microbiome diversity and composition affect microbiome stability during pathogen infection; (2) to determine how long-term temperature change affects the microbiome’s response to pathogen infection. The project will leverage the model organism Drosophila melanogaster for its tractability and relevance to human health and wild Drosophila species for their diversity and ecological realism. In Specific Aim 1, Hawaiian Drosophila species, which have naturally diverse microbiomes, will be used to identify relationships between microbiome structure (diversity and composition) and stability during infection by a bacterial pathogen. Next, causal relationships between microbiome structure and stability will be tested by manipulating the microbiome of D. melanogaster and exposing the flies to the pathogen. Specific Aim 2 will use populations of a single Drosophila species, which have naturally evolved under different temperatures, to test if adaptation to temperature affects how the microbiome and host respond to pathogen infection. In both specific aims, microbiome structure will be measured by DNA sequencing of microbial phylogenetic markers (16S, ITS), which identify the microbial taxa present and their relative abundances. Microbiome function will be assessed using shotgun metagenomics and transcriptomics, which predict functional capacity based on gene orthologues. Pathogen-induced microbiome perturbation will be measured as the change (before and after infection) in microbiome structure and function. Stability is the inverse of perturbation, i.e., the ability to avoid change despite disturbance. Effects of microbiome structure on stability will be determined by testing how microbiome structure prior to infection affects the magnitude of perturbation after infection. This project will generate knowledge on microbiome structure-stability relationships, which will provide a foundation for future research to understand the mechanisms underlying stability and resilience and consequences for host health.