An amazing diversity of microscopic wildlife inhabits the bodies of humans and other animals, with some of the densest microbial ecosystems on the planet thriving within the vertebrate intestine. Resident microbes have far-reaching impacts on the biology of their hosts, from promoting development and homeostasis to inciting infection and disease. Our lab uses transparent zebrafish as an animal model together with genetically engineered microbial communities and live imaging to spy on the inner workings of the gut microbiome. One of our overarching goals is to use what we discover to imagine new possibilities for therapeutically manipulating the microbiome to defend against pathogenic invaders, stop the spread of antibiotic resistance, and promote immune homeostasis. Our research program can be broken down into two main areas. The first area is focused on piecing together a broader picture of the life cycles and evolutionary trajectories of gut microbes. The second area is focused on understanding the mechanisms by which animal hosts shape resident microbial communities and sense their activity. Several ongoing projects in the Wiles lab operate at the intersection of these two research areas and aim to answer outstanding questions that concern how animal cells and tissues detect various properties of gut microbes (e.g., their abundance, localization, and behavior) and how immune tolerance to gut microbiota is maintained in the face of dramatic ecological and evolutionary fluctuations.