Engineering microbiota to optimize inter-host transmission

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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.