Engineering microbiota to optimize inter-host transmission

项目摘要/摘要（项目 2） 所有动物（包括人类）都是多种微生物的宿主，这些微生物统称为它们的微生物。 “微生物组”与他们的健康和福祉密切相关。操纵和管理 微生物组需要了解决定微生物组组成的力量。仅一小部分 宿主之间微生物组的变异可以通过个体宿主因素来解释，例如宿主遗传学或 饮食，导致人们认为没有管理微生物组组成的一般规则，并且 为了宿主健康而设计微生物组将非常困难。然而主机间传输，定义为 微生物在个体宿主之间的移动，有可能显着改变微生物组 组成。尽管研究历史悠久，但这一因素在微生物组研究中经常被忽视 证明病原体在个体宿主之间的传播可以影响多样性和功能 的病原体。主机间传输也有可能影响由主机调节的功能 微生物组，类似于疾病的传播。理论上，这个过程可以用来创建 “可传染的健康”，利用微生物传播来改善宿主健康，无需直接操纵 个人主机。为了有效地操纵主机间传输，了解主机间的驱动程序至关重要 主机间传输速率的变化，主机间传输发生变化的条件 对微生物组组成的最大影响以及对宿主间宿主的功能影响 传输。我们将通过结合实验来解决拟议研究中的每个主题 通过理论建模来确定宿主间的性质、驱动因素和后果 斑马鱼肠道微生物组的传播。相对简单的饲养方式和较大的离合器尺寸 斑马鱼使我们能够操纵微生物在大量复制品之间的传播 个体的规模在人类或其他脊椎动物模型中不可行。这些实验的结果将 在计算模型中合成，该模型将广泛适用于宿主微生物系统，包括 人类。拟议的研究将严格检验健康可以通过传播病毒的观点。 微生物组成员，对人类医学具有重要影响。

PROJECT SUMMARY/ABSTRACT (PROJECT 2) All animals (including humans) are host to a diverse collection of microorganisms, collectively known as their “microbiome,” which is intimately involved in their health and wellbeing. Manipulating and managing the microbiome requires understanding the forces that determine microbiome composition. Only a small fraction of microbiome variation across hosts can be explained by individual host factors, for example host genetics or diet, leading to the perception that there are no general rules governing microbiome composition and that engineering microbiomes for host health will be very difficult. However inter-host transmission, defined as the movement of microbes among individual hosts, has the potential to substantially alter microbiome composition. This factor is frequently overlooked in microbiome studies, despite a long history of research demonstrating that transmission of pathogens among individual hosts can influence the diversity and function of the pathogens. Inter-host transmission also has the potential to impact host functions modulated by the microbiome, analogous to the transmission of disease. This process could, in theory, be harnessed to create “transmissible health,” the use of microbial transmission to improve host health without direct manipulation of individual hosts. To effectively manipulate inter-host transmission, it is crucial to understand the drivers of variation in rates of inter-host transmission, the conditions under which inter-host transmission has the greatest impact on microbiome composition, and the functional consequences to the host of inter-host transmission. We will address each of these topics in the proposed research, by combining experimental manipulations with theoretical modeling to determine the nature, drivers and consequences of inter-host transmission of the zebrafish intestinal microbiome. The relatively simple husbandry and large clutch sizes of zebrafish allow us to manipulate transmission of microorganisms among a large number of replicate individuals at a scale not feasible in humans or other vertebrate models. The results of these experiments will be synthesized in a computational model that will be broadly applicable to host-microbe systems, including humans. The proposed research will rigorously test the idea that health can be transmitted via dispersal of microbiome members, with important implications for human medicine.