OBJECTIVES: THE OBJECTIVES OF THIS ROSBIO NEW INVESTIGATOR AWARD PROJECT ARE TO DETERMINE WHAT IMPACT THE SHIFT IN THE GUT MICROBIOME HAS ON THE FUNCTION OF THE LYMPHATIC AND IMMUNE SYSTEMS OF THE GASTROINTESTINAL TRACT. WE WILL ALSO DETERMINE IF THE RESTORATION OF A KEY METABOLITE HISTIDINE TO NORMAL LEVELS ALLEVIATES THE OBSERVED CHANGES. APPROACH: WE WILL USE A GROUND BASED MODEL OF FECAL TRANSPLANT FROM SPACE FLOWN ANIMALS INTO GNOTOBIOTIC ANIMALS TO ADDRESS HOST/ MICROBIOME INTERACTIONS. THIS MODEL HAS BEEN USED TO STUDY THE INFLUENCE OF THE MICROBIOME OF NUMEROUS PATHOLOGIES ON IMMUNE AND PHYSIOLOGICAL PARAMETERS. THIS TECHNIQUE HAS NOT BEEN APPLIED TO THE FIELD OF SPACE BIOLOGY AND PRESENTS AN OPPORTUNITY TO MEASURE THE INFLUENCE OF THE SPACE FLIGHT MICROBIOME ON THE HOST IN AN ENVIRONMENT ISOLATED FROM OTHER FACTORS SUCH AS MICROGRAVITY AND RADIATION. OUR TEAM WILL USE TECHNIQUES FROM THE IMMUNOLOGY AND PHYSIOLOGY FIELDS TO ADDRESS THE ISSUES OF IMPAIRED LYMPHATIC AND IMMUNE FUNCTION. THESE INCLUDE TECHNIQUES FOR MEASURING LYMPHATIC FUNCTION (TRANSPORT AND PERMEABILITY) UNIQUE TO OUR RESEARCH GROUP. WE WILL ALSO USE SPECIALIZED IMMUNE CELL ACTIVATION ASSAYS AND FLOW CYTOMETRY TO GAUGE THE CHANGES IN THE MUCOSAL IMMUNE SYSTEM OF THE GUT.