Combinatorial ecology in the simple fruit fly gut microbiome

The gut microbiome is an ecosystem within an animal host that impacts health and disease in mysterious ways. Complex interactions between individual species can produce unexpected results, often involving feedbacks with the host physiology. Discovering general principles of microbiome-host systems can benefit human health and also teach us about how groups of interacting organisms behave differently from their separate parts. To deconstruct this complexity, my lab develops a microbiome model using the fruit fly as the host and its natural set of just five stably colonizing gut bacteria as the microbiome. We reconstruct this system combinatorially, starting with germ-free flies, to ask how bacteria influence each other’s ability to colonize the gut and how these interactions influence physiology of the fly. We find that colonization ability of new species is strongly influenced by previous colonizers due both to spatial and metabolic interactions. These interactions also shape host fitness, altering the lifespan and reproduction of flies. We introduce new mathematical tools called epistatic filtrations to calculate microbiome interactions. The fly gut serves as an effective combinatorial model to dissect the gut microbiome.