THIS PROJECT AIMS TO BETTER OUR UNDERSTANDING OF THE MECHANISMS OF EARLY-LIFE STRESSORS ON GASTROINTESTINAL TRACT (GIT) HEALTH AND INFLAMMATION. AT PRESENT, PRE-WEANING MORTALITY IS UP TO 10%, WITH THE PRINCIPAL CAUSE OF DEATH BEING DIARRHEA. DIARRHEA IN YOUNG CALVES IS OFTEN CAUSED BY COMPROMISED GASTROINTESTINAL HEALTH AND INFLAMMATION. BY INVESTIGATING EARLY LIFE STRESSORS THAT PROMOTE INFLAMMATION AND OXIDATIVE STRESS, WE AIM TO IDENTIFY AND DEVELOP MANAGEMENT STRATEGIES THAT WILL REDUCE INCIDENCE OF DIARRHEA, REDUCING THE NEED FOR ANTIBIOTIC TREATMENTS, AND REDUCING MORBIDITY AND MORTALITY PRE-WEANING. OUR HYPOTHESIS IS THAT EARLY LIFE INSULTS SUCH AS EXCESSIVE TRANSPORTATION, LACK OF COLOSTRUM FEEDING WITHIN THE FIRST 36 H OF LIFE, OR ABRUPT WEANING AT EARLY AGES, COMPROMISE GIT HEALTH AND PROMOTE INFLAMMATORY STATUS. THESE WILL LEAD TO HEALTH ISSUES EARLY IN LIFE WITH MASSIVE ECONOMIC LOSSES AND COMPROMISED LIFELONG PRODUCTIVITY. OUR SPECIFIC OBJECTIVES ARE TO 1) DETERMINE ROLE OF EXCESSIVE TRANSPORTATION (&GT;300 MILES) ON GIT PERMEABILITY, OXIDATIVE STRESS, AND INFLAMMATION (NEONATAL STAGE), 2) DETERMINE ROLE OF VFA AND PH IN INFLAMMATORY STATE AND PERMEABILITY IN INTESTINAL EPITHELIAL CELLS (PRE-WEANING), AND 3) DETERMINE ROLE OF WEANING METHOD (ABRUPT VS. GRADUAL) ON LOCAL AND SYSTEMIC INFLAMMATION STATUS, OXYLIPIDS PROFILE, AND ANIMAL HEALTH. NUTRITIONAL AND MANAGEMENT STRATEGIES THAT HELP TO REDUCE THE OCCURRENCE OR SEVERITY OF DIARRHEA IN DAIRY CALVES POTENTIALLY WILL CREATE SOLUTIONS TO ONE OF THE COSTLIEST DISEASES IN THE DAIRY INDUSTRY, THUS ENHANCING ANIMAL HEALTH AS WELL AS PRODUCTIVITY AND ECONOMIC BENEFITS FOR DAIRY FARMERS.