CAMPYLOBACTER IS A MAJOR FOODBORNE PATHOGEN IN THE U.S. AND WORLDWIDE, AND IS TRANSMITTED TO HUMANS PRIMARILY BY CONSUMPTION OF CONTAMINATED CHICKEN MEAT. BIRDS ARE FREQUENTLY COLONIZED BY CAMPYLOBACTER IN THE INTESTINAL TRACT AND MANY BROILER FLOCKS CARRY THE ORGANISM AT THE SLAUGHTER AGE, WHICH LEADS TO FREQUENT CARCASS CONTAMINATION IN PROCESSING PLANTS. INDEED, A RECENT STUDY RANKED CAMPYLOBACTER IN POULTRY AS THE HIGHEST PATHOGEN-FOOD COMBINATION WITH THE LARGEST BURDEN ON PUBLIC HEALTH CONSIDERING THE NUMBER OF CASES, HOSPITALIZATION, DEATH, ECONOMIC COST, AND HEALTH-RELATED QUALITY OF LIFE IN THE U.S. ALTHOUGH SIGNIFICANT KNOWLEDGE HAS BEEN GAINED REGARDING THE ECOLOGY AND EPIDEMIOLOGY OF CAMPYLOBACTER IN POULTRY, EFFECTIVE INTERVENTION STRATEGIES FOR THE CONTROL OF CAMPYLOBACTER IN THE FOOD CHAIN ARE STILL LACKING. OUR RECENT LONGITUDINAL STUDY ON COMMERCIAL BROILER FARMS (INVOLVING 406 FLOCKS RAISED ON 15 FARMS FOR ABOUT 2 YEARS) REVEALED A STARK DIFFERENCE IN CAMPYLOBACTER PREVALENCE. SPECIFICALLY, SOME FARMS WERE FOUND CONSISTENTLY CAMPYLOBACTER-FREE, WHILE OTHERS WERE ALWAYS CAMPYLOBACTER-POSITIVE DESPITE THE FACT THAT ALL THE FARMS OPERATED UNDER THE SAME VERTICAL INTEGRATION SYSTEM AND UTILIZED SIMILAR PRODUCTION AND MANAGEMENT PRACTICES. FURTHERMORE, OUR PRELIMINARY RESULTS REVEALED SIGNIFICANT DIFFERENCES IN THE GUT MICROBIOTA COMPOSITIONS BETWEEN CAMPYLOBACTER -NEGATIVE AND CAMPYLOBACTER -POSITIVE FARMS AS DETERMINED BY 16S RRNA GENE SEQUENCING OF CECAL MICROBIOTA. WE THUS HYPOTHESIZE THAT THE INTESTINAL MICROBIOTA MAY INFLUENCE CAMPYLOBACTER COLONIZATION IN POULTRY. IN ORDER TO DEVELOP MICROBIOTA-BASED INTERVENTIONS FOR CONTROLLING CAMPYLOBACTER IN POULTRY, WE HAVE DEVELOPED A 3-YEAR PROJECT WITH THE FOLLOWING TWO SPECIFIC AIMS: 1) IDENTIFYING THE SPECIFIC DIFFERENCES IN THE INTESTINAL MICROBIOTA BETWEEN CAMPYLOBACTER-POSITIVE AND CAMPYLOBACTER-NEGATIVE FLOCKS BY DETERMINING AND COMPARING THE CECAL MICROBIOTA AND METABOLOMES IN ADULT BROILER CHICKENS FROM EACH FARM CATEGORY, AND 2) DESIGNING AND EVALUATING MICROBIOTA-BASED INTERVENTIONS FOR MITIGATING CAMPYLOBACTER COLONIZATION IN CHICKENS BY ASSESSING IF THE BIRDS FROM EACH FARM CATEGORY HAVE DIFFERENT SUSCEPTIBILITY LEVEL TO CAMPYLOBACTER AND IF THE GUT MICROBIOTA FROM CAMPYLOBACTER-FREE FARMS CAN REDUCE OR ELIMINATE CAMPYLOBACTER COLONIZATION USING IN VIVO STUDIES AS WELL AS IN VITRO EXPERIMENTS FOR ASSESSMENT OF THE ANTI-CAMPYLOBACTER ACTIVITY OF THE COMMENSAL GUT MICROBIOTA. THE PROPOSED WORK WILL DEVELOP EFFECTIVE PREHARVEST INTERVENTIONS AGAINST CAMPYLOBACTER ON POULTRY FARMS AND DIRECTLY ADDRESSES THE PRIORITY AREA ("DEVELOP STRATEGIES TO REDUCE FOODBORNE CONTAMINANTS IN FOOD OR THE ENVIRONMENT AT ANY POINT ALONG THE FOOD SUPPLY CHAIN") OF PROGRAM A1331. THE ACTIVITIES ARE EXPECTED TO CONTRIBUTE SIGNIFICANTLY TO IMPROVING FOOD SAFETY.