Diet is thought to be a major environmental factor contributing to Inflammatory Bowel Disease (IBD) and represents a non-invasive path to improve this debilitating condition. To leverage diet to treat IBD the precise ways that dietary components influence development or healing of inflammation need to be determined. We discovered that different dietary protein sources have variable effects on intestinal inflammation and these effects are dependent on the community of microorganisms (microbiome) that inhabit the human colon. In particular, we discovered that soy protein promotes production of a beneficial metabolite called isobutyrate that reduces inflammation in a mouse model of IBD that we developed to mimic low fiber diet- and microbiome-driven inflammation. Isobutyrate is only produced by some bacteria and is derived from the dietary amino acid L-valine via at least two different metabolic pathways. Because soy protein specifically promotes isobutyrate, our model is that it is better at delivering L-valine-containing peptides to the colon after digestion, leading to bacterial isobutyrate production. The proposed experiments will uncover the specific component(s) of soy protein that promotes isobutyrate as well as the bacteria that produce this metabolite so that dietary protein can be optimized in the context of patients’ microbiomes to reduce inflammation.