THE DIVERSE COMMUNITIES OF MICROBES THAT RESIDE IN THE HUMAN INTESTINAL TRACT PLAY CRITICAL ROLES IN THE PREVENTION OF ENTERIC INFECTION FOR BOTH ASTRONAUTS AND THE GENERAL PUBLIC. A COMPREHENSIVE UNDERSTANDING OF HOW CHANGES IN GUT MICROBIOTA COMPOSITION IMPACTS SUSCEPTIBILITY TO INFECTION HAS BEEN LIMITED BY A LACK OF COST-EFFECTIVE PHYSIOLOGICALLY RELEVANT INFECTION MODELS CONTAINING BOTH HUMAN HOST AND MICROBIAL CELLS. WE PREVIOUSLY DEVELOPED AN ADVANCED THREE-DIMENSIONAL (3-D) MODEL OF HUMAN COLON CONTAINING INFLAMMATORY IMMUNE CELLS AND APPLIED IT TO STUDY HOST-PATHOGEN INTERACTIONS INCLUDING THE INFLUENCE OF LOW FLUID SHEAR MICROGRAVITY ANALOGUE CULTURE ON THE ABILITY OF THE ENTERIC PATHOGEN SALMONELLA TO COLONIZE THE HOST. THIS SAME MODEL WAS ALSO APPLIED TO STUDY HOSTMICROBIOTA INTERACTIONS USING PATIENT-DERIVED FECAL CONSORTIA FROM BOTH HEALTHY INDIVIDUALS AND THOSE SUFFERING FROM A GASTROINTESTINAL DISORDER. FOR THE PROPOSED STUDY OUR GOAL IS TO POPULATE OUR 3-D INTESTINAL CO-CULTURE MODEL CONTAINING IMMUNE CELLS WITH ASTRONAUT FECAL MICROBIOTA (PREVIOUSLY COLLECTED DURING THE MICROBIOME SPACEFLIGHT EXPERIMENT) AND ASSESS ITS INFLUENCE ON INFECTION WITH SALMONELLA CULTURED UNDER MICROGRAVITY ANALOGUE CONDITIONS. THE OUTCOME OF THESE INTERACTIONS WILL BE PROFILED USING A VARIETY OF APPROACHES INCLUDING COLONIZATION STUDIES MICROSCOPY METABOLOMICS 16S ANALYSIS AND CYTOKINE ANALYSIS. THE FOODBORNE PATHOGEN SALMONELLA WAS SELECTED AS THE MODEL PATHOGEN AS IT IS A LEADING CAUSE OF GASTROINTESTINAL DISEASE WORLDWIDE AND IMPOSES AN ENORMOUS HEALTH AND SOCIOECONOMIC BURDEN. FROM NASAS PERSPECTIVE SALMONELLA IS CONSIDERED A POTENTIAL SOURCE OF INFECTION DURING SPACEFLIGHT THAT COULD INCAPACITATE CREW MEMBERS DURING A MISSION. DUE TO ITS ROUTE OF ACCESS THROUGH SPACEFLIGHT FOOD NASA SPECIFICALLY TESTS FOR SALMONELLA PRIOR TO FLIGHT AND HAS PREVIOUSLY DISQUALIFIED FOOD DESTINED FOR THE ISS BASED ON THE ISOLATION OF THIS PATHOGEN. THE PROPOSED MICROGRAVITY ANALOGUE STUDIES COMBINE MICROBIOLOGY TISSUE ENGINEERING AND PHYSICS TO PROVIDE NEW INSIGHT INTO THE INFLUENCE OF SPACEFLIGHT ON HOST-MICROBIOME INTERACTIONS AND THE ABILITY TO PROTECT AGAINST PATHOGEN INFECTION WITH APPLICATIONS FOR THERAPEUTIC DEVELOPMENT FOR SPACEFLIGHT EXPLORATION AND HEALTH OF THE GENERAL PUBLIC.