How do hosts control microbiome dynamics?

Mammalian microbiomes are dynamic ecosystems, composed of hundreds of taxa whose populations continuously rise and fall, shaped by interactions microbes have with their host and one another. Understanding the forces driving microbiome dynamics is critical if we wish to engineer them, however, the vast complexity of most microbiomes renders this a formidable challenge. I will address this challenge, developing interdisciplinary tools to understand and predict microbiome dynamics, focusing on the poorly understood role of the host in controlling microbiome dynamics. First, I will use innovative sequencing tools to quantify the impact of host immune background on the assembly and stability of the gut microbiome, then develop new computational tools to identify the specific host-to-microbe interactions causatively driving these differences. Concurrently, I will develop new computational tools to identify microbe-to-host interactions shaping host immune development. Finally, I will build a new body of theory to understand how these interactions integrate to shape overall microbiome dynamics. Throughout, I will focus on one key host adaptation: Immunoglobulin A. However, by combining targeted experimental and computational approaches with novel theory I will build an interdisciplinary platform for investigating the role of any host mechanism. Together this will transform our understanding of microbiome dynamics.