Project Summary The short chain fatty acid butyrate is a key molecule in the human gut metabolome, regulating bacterial growth, inflammation, and colon cell health. Despite its importance there is currently no reliable method for inline monitoring of butyrate production in situ. In addition, cecal and fecal levels of butyrate are often not good predictors of butyrate production by gut bacteria. The goal of this proposal is to build bacterial biosensors for butyrate which, coupled to cellular memory circuits, will enable monitoring of butyrate content throughout the small and large intestine and biogeographical mapping of butyrate concentrations. This technology will allow researchers to test many different interventions (e.g., prebiotics, probiotics, and other forms of butyrate supplementation) with the goal of optimizing the levels of butyrate in the gut. We will also test interventions that increase butyrate as a proof of concept of the method.