Engineering microbiota to optimize inter-host transmission

项目摘要/摘要(项目2) 所有动物(包括人类)都是各种微生物的宿主，统称为他们的 “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 微生物组在不同寄主之间的变异可以由单个寄主因素来解释，例如寄主遗传学或 饮食，导致人们认为微生物群的组成没有一般规则，而且 为宿主健康设计微生物群将是非常困难的。但是，主机间传输被定义为 微生物在各个寄主之间的移动，有可能显著改变微生物群 组成。尽管有很长的研究历史，但这一因素在微生物组研究中经常被忽视 证明病原体在个体寄主之间的传播可以影响多样性和功能 病原体的数量。主机间传输也有可能影响由 微生物群，类似于疾病的传播。从理论上讲，这个过程可以被利用来创造 “可传播的健康”，利用微生物传播来改善宿主健康，而不需要直接操作 单个主机的数量。要有效地控制主机间传输，了解的驱动程序至关重要 主机间传输速率的变化，主机间传输具有 对微生物群组成的影响最大，以及寄主间对宿主的功能后果 变速箱。我们将在拟议的研究中通过结合实验来解决这些主题 通过理论建模确定主机间的性质、驱动因素和后果的操作 斑马鱼肠道微生物群的传播。相对简单的饲养和较大的离合器尺寸 斑马鱼允许我们操纵微生物在大量复制之间的传播 这种规模的个体在人类或其他脊椎动物模型中是不可行的。这些实验的结果将 在将广泛适用于宿主-微生物系统的计算模型中合成，包括 人类。这项拟议的研究将严格检验健康可以通过传播的方式传播的观点。 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.