Abstract The Institute for Translational Medicine (ITM) at the University of Chicago (UChicago) proposes to purchase and install a large and flex indirect calorimeter (IC) to support leading research programs in metabolism, diabetes, obesity, disorders of thyroid function, the microbiome, inflammatory bowel disease, weight reduction, frailty, circadian biology, and kidney disorders, among others. IC is the gold standard for measuring energy expenditure (EE) providing precise and accurate measures under regulated environmental conditions, ranging from maximal physical activity to sleep (SMR). For over 15 years UChicago investigators have measured EE using metabolic carts and doubly-labelled water, which only measures resting EE or RMR, for a limited duration (maximum 4 hours), requiring an over-the-head hood placement, limiting free mobility and with less precision than IC. Despite these limitations, UChicago NIH-funded investigators have incorporated measures of EE since 2004 resulting in highly impactful scientific findings. The IC proposed in this application is the only equipment available for long term (24hrs or more) EE measurements, that can determine circadian EE (ie RMR vs. SMR) with strictly controlled environmental conditions while aspects of daily life are evaluated including eating or thermal effects of food (TEF), sleeping (SMR) and physical activity. With the establishment of the Microbiome Center in 2015 and the Duchossois Family Institute in 2017 at UChicago, world-leading programs in the microbiome in health and disease are now being established. There is strong evidence for the impact of the microbiome on EE in a variety of complex medical disorders such as obesity, anorexia, metabolic syndrome, diabetes, circadian biology, chronic kidney disease, post COVID 19 syndromes, congestive heart failure and inflammatory bowel disease. However, EE changes associated with these disorders are nuanced and limitations in precision and accuracy require better instrumentation. Use of the IC proposed in this application will help to optimize patient long-term health in a variety of medical settings. By having capacity for IC measurement of EE while collecting biofluids simultaneously in a controlled environment, the contributory roles of the microbiome, metabolism and circadian biology can be characterized. Through the ITM, a multi-institution CTSA program partnered with Rush University and affiliated with Loyola University, Northshore Hospital, Advocate Center and the Illinois Institute for Technology, city-wide utilization of the IC will be facilitated and supported. Investigators from other Chicago- based institutions including Northwestern University and University of Illinois, and regional or great lakes such as University of Wisconsin and the Nutrition Obesity Research Center (NORC) investigators from University of Michigan, will perform scientific investigations. Seminars with experienced investigators in EE from other sites will advanc...