THERE IS NOW A STRONG CONSENSUS THAT THE GUT MICROBIOME IS A CRUCIAL DETERMINANT OF HOST PHYSIOLOGY AND HEALTH. IT IS ALSO CLEAR THAT PERTURBING THIS COMMUNITY WITH ANTIBIOTICS CAN HAVE VASTLY NEGATIVE HEALTH CONSEQUENCES RANGING FROM CLOSTRIDIODES DIFFICILE COLITIS TO CHRONIC CONDITIONS SUCH AS OBESITY AND AUTOIMMUNE DISEASES. THUS, AS WE WORK TO IMPROVE ANTIMICROBIAL THERAPY, WE MUST DEVELOP TREATMENT METHODOLOGIES THAT TARGET PATHOGENS WHILE PRESERVING THE OVERALL STRUCTURE AND FUNCTION OF THE MICROBIOME FROM ANTIBIOTIC-INDUCED DYSBIOSIS. DIETARY FIBER IS A KEY POSITIVE DETERMINANT OF MICROBIOME METABOLISM AND COMPOSITION. RECENT DATA FROM OUR GROUP INDICATE THAT THE METABOLIC ACTIVITY OF THE MICROBIOME IS A CRUCIAL DETERMINANT OF ANTIBIOTIC-INDUCED MICROBIOME DISRUPTION AND THAT PURIFIED FIBER PROVIDES PREBIOTIC PROTECTION TO THIS COMMUNITY DURING TREATMENT. SINCE FIBER IS NOT TYPICALLY CONSUMED IN THE PURIFIED FORM, IN THIS GRANT WE WILL PROFILE THE IMPACT OF THREE KEY COMMODITYGRAINS WITH HIGH FIBER CONTENT, FIELD CORN, WHOLE GRAIN WHEAT AND WHOLE GRAIN OATS, ON THE COMPOSITION OF THE MURINE MICROBIOME AND ITS RESPONSE TO ANTIBIOTICS. WE HYPOTHESIZE THAT SUPPLEMENTATION WITH THESE GRAINS WILL REDUCE THE DETRIMENTAL IMPACT OF ANTIBIOTICS ON THE MICROBIOME AND PROMOTE RECOVERY AFTER TREATMENT. WE WILL ALSO TEST IF THIS PROTECTION IS ASSOCIATED WITH IMPROVED HOST HEALTH INDICATORS SUCH AS: GUT BARRIER FUNCTION, REDUCED INFLAMMATORY RESPONSE, AND ELEVATED PROTECTION FROM ENTERIC PATHOGENS. IN THE LONG-TERM, IDENTIFYING PREBIOTIC WHOLE GRAINS WHICH ARE CAPABLE OF REDUCING ANTIBIOTIC-ASSOCIATED COMPLICATIONS WILL, IN TURN, PROMOTE THE CONSUMPTION OF THESE AGRICULTURALLY IMPORTANT GRAINS AND IMPROVE HUMAN HEALTH.