Dissecting host and microbial contributions to gut microbiome homeostasis

项目摘要 该项目的目标是了解宿主生理学、微生物代谢和 肠道生态相互作用，以确定肠道微生物组动力学和肠道稳态的背景下，饮食 变化量肠道微生物在食物的消化、营养物质的获取和防御疾病中起着关键作用。 病原体杂食动物的肠道微生物群必须能够维持体内平衡， 这些功能在面对多样化和可变的宿主饮食时发挥作用。我们建议培育杂食性蟑螂 作为一种新的模式系统，用于识别和表征宿主和微生物对饮食变化的反应。 蟑螂在昆虫中是不寻常的，因为它们拥有高度多样化的后肠微生物群， 在分类学和功能上类似于人类的结肠微生物区系。这个财产，连同他们的沿着 易于实验和饮食操作，使它们成为研究的理想低成本昆虫模型 肠道微生物组的稳态和生态失调。我们发现蟑螂的肠道微生物群 高度稳定，个体间变异性低，在分类学上表现出最小变异 面对饮食结构的重大变化，我们假设这种稳定性可能是由于 1)宿主-微生物代谢交叉喂养2）稳定肠道之间的相互作用和代谢共依赖性 微生物或3）蟑螂肠道微生物的高度代谢灵活性。这些假设不是 相互排斥，多个机制可能协同行动。我们将使用一个 分子和实验方法的结合。我们将利用宏基因组学和元转录组学 研究蟑螂肠道转录和代谢网络的技术，以及它们如何响应 饮食变化我们还将建立一个丰富的、具有重要生态意义的蟑螂肠道培养库 微生物研究肠道微生物代谢能力，基因组变异和营养依赖性。关注- UP研究将利用知生昆虫来研究宿主-微生物和微生物-微生物之间的相互作用， 示范社区，并将纳入行为干预，以评估环境的作用， 传播和社会行为在塑造肠道微生物组动态中的作用。总之，这些努力将扩大我们的 了解宿主和微生物对肠道稳态的贡献，并将使新的 以及改变人类肠道微生物组结构和功能的改进策略。

Project Summary The goal of this project is to understand how interactions between host physiology, microbial metabolism and gut ecology interact to determine gut microbiome dynamics and gut homeostasis in the context of dietary variation. Gut microbes play key roles in the digestion of food, acquisition of nutrients, and defense against pathogens. The gut microbiota of omnivores must be able to maintain homeostasis and continue to carry out these functions in the face of a diverse and variable host diet. We propose to develop omnivorous cockroaches as a new model system for identifying and characterizing host and microbial responses to dietary shifts. Cockroaches are unusual among insects in that they host a highly diverse hindgut microbiota that is taxonomically and functionally analogous to the colonic microflora of humans. This property, along with their tractability to experimental and dietary manipulation, makes them ideal as a low-cost insect model for the study of gut microbiome homeostasis and dysbiosis. We have discovered that the gut microbiota of cockroaches is highly stable, with low individual-to-individual variability and exhibiting minimal variation in taxonomic profile in the face of major alterations in dietary composition. We hypothesize that this stability may be due to 1) host-microbe metabolic cross-feeding 2) stabilizing interactions and metabolic co-dependencies among gut microbes or 3) a high degree of metabolic flexibility in cockroach gut microbes. These hypotheses are not mutually exclusive, and multiple mechanisms may be acting in concert. We will test these hypotheses using a combination of molecular and experimental approaches. We will utilize metagenomic and metatranscriptomic techniques to study cockroach gut transcriptional and metabolic networks and how they change in response to dietary variation. We will also develop a culture library of abundant and ecologically important cockroach gut microbes to study gut microbial metabolic capabilities, genome variation, and nutritional dependencies. Follow- up studies will utilize gnotobiotic insects to study host-microbe and microbe-microbe interactions in simplified model communities, and will incorporate behavioral interventions to evaluate the role of environmental transmission and social behavior in shaping gut microbiome dynamics. Together, these efforts will extend our understanding of host and microbial contributions to gut homeostasis, and will enable the development of new and improved strategies to alter gut microbiome structure and function in humans.