EARLY LIFE FACTORS SHAPING DEVELOPMENT OF INTESTINAL NUTRIENT TRANSPORT IT�S RELATION TO IMMUNE DEVELOPMENT IN EARLY WEANED PIGS

The overall goal of this project is to determine how commone early life production stressors in the pig (e.g. early weaning) impact long-term development of intesinal nutrient transport function and how these changes interact with immune develop and function throughout the production lifespan.Our central hypothesis is that early weaning induces mast cell activation during a critical period of GI development which alters the normal development and function of select glucose and amino acid (AA) transporter systems leading to chronic inflammation and suboptimal performance and feed efficiency. We will test this central hypothesis in 3 specific aims:AIM 1: Test the hypothesis that early weaning alters the normal trajectory of select glucose and AA transporters in the gut and immune system which corresponds with impaired performance and stress resiliency from wean to finish. Our preliminary studies demonstrate that early weaning affects the function and partitioning of select glucose and AA transporters. We will combine electrophysiology and molecular biology approaches to define the precise programming effects of early weaning on gut epithelial, immune cell and adipocyte glucose and AA transporter expression and functionAIM 2: Test the hypothesis that intestinal mast cell mediators are modulators of intestinal epithelial glucose and AA transport. Mast cells are localized in close proximity to the intestinal epithelium and are immediately activated upon exposure to psychological stress. We will determine the role of mast cells and select mast cell mediators on stress-induced alterations in glucose and glucose and AA transport in the porcine intestine.AIM 3: Test the hypothesis that early targeting of mast cell activation promotes the development and lifetime function of gut and immune nutrient transporters and wean to finish performance. Early weaning induces mast cell activation and mediator release (e.g. histamine, proteases, TNF, etc) during a critical period of postnatal gut development, which we hypothesis leads to long-term alterations in intestinal nutrient transporter development and function. We will test whether targeted inhibition of mast cells and mast cell mediators during the critical weaning period enhances lifetime nutrient transporter efficiency, nutrient partitioning and performance in early weaned pigs.