Microbial Engineering to Control the Structure and Function of the Gut Microbiome.

微生物工程控制肠道微生物组的结构和功能 总结 人体微生物群，即生活在人体上和体内的微生物的集合，与人体完全整合。 生理学，并已广泛涉及健康和疾病。与所有微生物群落一样， 环境、细菌间和界间相互作用的总和控制着细菌的组成和 微生物群的功能。到目前为止，自上而下的方法主要用于研究微生物组 功能，使用多组学技术绘制微生物分类群，基因和代谢物之间的相关性 在不同的环境条件下具有功能特性。虽然这些研究提供了丰富的 假设，需要自下而上的方法来确定因果关系的分子机制， 微生物与它们的环境相互作用，相互作用，以及宿主。这些机制研究的综合 可以进一步实现预测模型，可以利用这些模型来设计微生物组。通过 新技术的开发和应用，本文所述的研究计划旨在预测 在肠道微生物组中设计生态反应和代谢功能。确定的微生物群落 反映自然群落的系统发育和功能多样性将被用作模型的测试平台 细菌间相互作用的结果所产生的现象。从自然中汲取灵感 微生物群落为合成生物学方法提供燃料，我们将创造新的工具， 操纵和表达控制在以前难以处理的肠道共生体。这些基因工具将应用于 将微生物基因和相关功能与微生物群落的新兴特性联系起来，包括 对环境扰动和小鼠肠道代谢网络的适应性。这些研究将提供一个 一个实验框架，用于研究构成微生物群落的核心功能 并为合理的微生物工程建立设计规则。

Microbial Engineering to Control the Structure and Function of the Gut Microbiome SUMMARY The human microbiota, the collection of microbes that live on and in the body, is fully integrated with human physiology and has been extensively implicated in health and disease. As with all microbial communities, the summation of environmental, interbacterial, and interkingdom interactions governs both the composition and function of the microbiota. To date, top-down approaches have been largely used to study microbiome function, using multi-omics techniques to draw correlations between microbial taxa, genes, and metabolites with functional properties in different environmental conditions. While these studies contribute a rich set of hypotheses, bottom-up approaches are required to causally pinpoint the molecular mechanisms through which microbes interact with their environment, one another, and the host. Synthesis of these mechanistic studies can further enable predictive models that can be leveraged to engineer microbiomes. Through the development and application of novel technologies, the research program described herein aims to predictively engineer ecological responses and metabolic functions in the gut microbiome. A defined microbial community that mirrors the phylogenetic and functional diversity of natural communities will be used as a testbed to model the emergent phenomena that arise as a result of interbacterial interactions. Using inspiration from natural microbial communities to fuel synthetic biology approaches, we will create new tools to allow for genetic manipulation and expression control in previously intractable gut symbionts. These genetic tools will be applied to link microbial genes and associated functions with emergent properties of microbial communities, including resilience to environment perturbations and metabolic networks in the mouse gut. These studies will provide an experimental framework to pursue investigations into the core functions that structure microbial communities and to establish design rules for rational microbiome engineering.