**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** POST-WEANING DIARRHEA (PWD) CAUSED BY THE BACTERIUM 'ENTEROTOXIGENIC ESCHERICHIA COLI' (ETEC) IS AN ECONOMICALLY IMPORTANT DISEASE IN WEANED PIGLETS. CURRENTLY, ANTIBIOTICS ARE USED IN THE SWINE INDUSTRY TO CONTROL INTESTINAL INFECTIONS, INCLUDING PWD IN PIGLETS. RECENT STUDIES HAVE CONFIRMED THAT DISRUPTION OF THE NORMAL GUT BACTERIAL COMMUNITIES (GUT MICROBIOME) INDUCED DURING WEANING TRANSITION IS A CRITICAL FACTOR INVOLVED IN THE DEVELOPMENT OF PWD. DISRUPTION OF THE NORMAL GUT MICROBIOME (GUT DYSBIOSIS) HAS BEEN FOUND TO BE INVARIABLY IMPLICATED IN BOTH INITIATION AND CLINICAL MANIFESTATION OF PWD. THEREFORE, STABILIZING THE GUT MICROBIOME DURING THE WEANING TRANSITION COULD BE AN EFFECTIVE STRATEGY FOR CONTROLLING PWD. RECENTLY, FECAL MICROBIOME TRANSPLANTATION (FMT) HAS BEEN SHOWN TO PREVENT GUT-DYSBIOSIS AND CONTROL SERIOUS INTESTINAL ILLNESSES IN HUMANS. HOWEVER, THE APPLICATION OF THESE STRATEGIES IS MINIMALLY EXPLORED IN THE SWINE INDUSTRY. THIS PROPOSAL SEEKS TO OPTIMIZE FMT IN SWINE AND TO UNDERSTAND THE MECHANISMS BY WHICH IT CONTROL GUT DYSBIOSIS AND ETEC INFECTION IN WEANING PIGLETS. IN THIS PROJECT, WE WILL TEST OUR CENTRAL HYPOTHESIS THAT GUT MICROBIOME DYSBIOSIS AND PWD IN PIGLETS COULD BE PREVENTED BY THE TRANSPLANTATION OF ADULT PIG GUT MICROBIOTA OF VARYING COMPLEXITY. IN THE LONG TERM, OUR RESULTS WILL HELP TO IMPROVE THE RATIONAL DESIGN OF DEFINED GUT BACTERIA MIX AS AN ALTERNATIVE TO ANTIBIOTICS TREATMENT IN PIGS. IN SUMMARY, THIS PROJECT SEEKS TO DEVELOP A GUT MICROBIOTA BASED INTERVENTION AS A NON-ANTIBIOTIC ALTERNATIVE TO CONTROL PWD -A SIGNIFICANT CHALLENGE IS COMMERCIAL SWINE PRODUCTION.