Project Summary Our circadian clocks synchronize physiological processes and behaviors like eating and sleeping to environmental light cycles. The central clock located in the brain attunes peripheral clocks located throughout the body to daily rhythms in environmental light. This systems level coordination of biological processes extends across all cell types and tissues and drives synchronization of whole-body metabolism. Recent work indicates that these biological timers also synchronize functions of our gut microbiome to daily rhythms in our feeding behavior. Given the essential role that the gut microbiome plays in nutrient acquisition, tuning the metabolic functions of the microbiome with the rhythms of the animal host is logical. However, the underlying mechanisms by which animal and microbial metabolism are synchronized, and the extent to which this synchronization impacts animal physiology is not well understood. I propose to address this evidence gap by investigating how circadian clocks and feeding rhythms promote oscillations in microbiome composition and function and how these oscillations in microbial function impact host physiology. We have discovered a key mechanism whereby the circadian clock may coordinate host and microbial metabolism through the regulation of multiple antimicrobial proteins (AMPs). These proteins produced by the epithelial cells in the intestine, have previously been shown to tailor the composition of the microbiome. This discovery has prompted two questions. First, how do rhythms in distinct AMPs shape the composition and metabolic functions of the microbiome across the day-night cycle. Second, how does the arrhythmic production of AMPs impact host physiology. To address these questions, my lab will employ an interdisciplinary approach that incorporates emerging technologies with metabolomics, gnotobiotic mouse models, and bacterial genetics.