Engineering microbiota to optimize inter-host transmission

项目总结/摘要（项目2） 所有动物（包括人类）都是各种微生物的宿主，这些微生物统称为微生物。 "微生物组"，这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。只有一小部分 微生物组在宿主间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，导致人们认为微生物组组成没有一般规则， 为宿主健康设计微生物组将非常困难。但是主机间传输，定义为 微生物在个体宿主之间的移动，有可能大大改变微生物组 混合物.这个因素在微生物组研究中经常被忽视，尽管研究历史悠久 证明病原体在个体宿主之间的传播可以影响生物多样性和功能， 的病原体。宿主间的传播也有可能影响宿主的功能， 微生物组，类似于疾病的传播。理论上，这个过程可以用来创造 “可传播的健康”，即利用微生物传播来改善宿主健康，而无需直接操作 的个别主机。为了有效地操纵主机间传输，了解 宿主间传播速率的变化，宿主间传播具有 对微生物组组成的最大影响，以及宿主间的功能性后果 传输我们将在拟议的研究中讨论这些主题，通过结合实验， 操纵与理论建模，以确定性质，司机和后果的主机间 斑马鱼肠道微生物组的传播。相对简单的饲养和大的离合器大小， 斑马鱼使我们能够操纵微生物在大量复制体之间的传播， 在人类或其他脊椎动物模型中不可行的规模的个体。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 人类这项拟议中的研究将严格测试健康可以通过传播的想法， 微生物组成员，对人类医学具有重要意义。

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.