Autoimmune diseases are debilitating and often life-threatening conditions that afflict a substantial minority of the human population. Aside from some known genetic variations, the causes of autoimmunity remain unclear, as does the reason for the rise in disease prevalence in Western countries. Recent studies of the human microbiome implicate various microbes and microbial proteins in the development of and response to autoimmune diseases. In collaboration with Dr. Katie Pollard’s group, we aim to improve understanding of the relationship between the microbiome and autoimmune disease by investigating how the microbiome interacts with its host over the time course of disease onset and progression. These studies use a mouse model of inflammatory bowel disease (IBD), because this system enables us to conduct carefully controlled experiments and to probe early, pre-symptomatic time points that are not easily accessible in human clinical studies. We are using shotgun metagenomic sequencing to explore the relationship between gut microbial communities and autoimmune disease. This technique, coupled with cutting-edge bioinformatics tools, allows us to profile the microbiome’s protein repertoire. We will generate protein profiles from birth through severe IBD and use statistical tests to compare these disease profiles to the profiles of healthy mice. These results are being analyzed in the context of temporal immunological data from the same mice. Our findings will then be related to metagenomic studies of IBD in humans. The goal of this study is to clarify the relationship between IBD and the mammalian gut microbiome. We aim to identify microbial proteins that predict IBD onset and temporally correlate with host immunological response to the disease. These biomarkers could be used to develop inexpensive early-onset and temporal diagnostics of IBD. Our analysis of the proteins and pathways that characterize IBD will also provide insight into possible mechanisms of disease induction. Finally, this study will establish the feasibility of using mouse models to study the role of the microbiome in human autoimmune disease and ultimately to develop microbiome-based therapeutics.