Guillemin, KarenVanBegue, STEPHANIE2022-10-262022-10-262022-10-26https://hdl.handle.net/1794/27740Animals are colonized by a consortium of microbes that sense and respond to their immediate environments. These microbes, collectively called the gut microbiota, promote epithelial proliferation in a diversity of animal hosts. While the effect of this relationship is well established, the mechanism underlying this response is less understood. In this work, we establish a molecular connection between colonization by the microbiota and the resulting increase in gut epithelial proliferation. We show that different homologs of a highly conserved chitin degrading enzyme promote epithelial proliferation in both zebrafish and fruit flies. Probing the mechanism of this conserved relationship in flies, we show that other enzymes that compromise the chitin lining of the gut will also stimulate epithelial proliferation. Finally, we find that proliferation is a result of innate immune sensing of increased concentration of luminal GlcNAc monomers which are the product of chitin-cleaving enzymes. The comparative work presented in this dissertation explores a new way of thinking of host-microbiome relationships that focuses on microbial function over identity or abundance of specific species.en-USAll Rights Reserved.Gut epithelial proliferationHost microbiome interactionsElectronic Thesis or Dissertation