OUR LONG-TERM GOAL IS TO UNDERSTAND THE INTERPLAY BETWEEN NUTRITION AND GUT HEALTH USING A PORCINE MODEL OF ISCHEMIC INTESTINAL INJURY TO INVESTIGATE MECHANISMS OF MUCOSAL REPAIR. IN PRELIMINARY STUDIES, WE HAVE SHOWN THAT DIETARY PROVISION OF ARACHIDONATE (ARA) TO NEONATES WITH ISCHEMIC INTESTINAL INJURY HASTENS REPAIR. NONETHELESS, RECOVERY OF INJURED MUCOSA REMAINS MARKEDLY IMPAIRED IN NEONATES COMPARED TO JUVENILE ANIMALS. THIS LED US TO INVESTIGATE OLIGOSACCHARIDES, WHICH ALTER THE MICROBIOME TO INDUCE MATURATION OF ENTERIC NEURAL ELEMENTS INVOLVED IN GUT BARRIER FUNCTION. OUR CENTRAL HYPOTHESIS IS THAT INTESTINAL REPAIR OF ISCHEMIC INJURY IN PORCINE NEONATES CAN BE SYNERGISTICALLY RESCUED BY A COMBINATION OF (1) DIETARY OLIGOSACCHARIDES, THAT WILL INTERACT WITH THE MICROBIOME TO ACCELERATE DEVELOPMENT OF THE MUCOSAL EGC NETWORK AND THUS INCREASE THE BIOAVAILABILITY OF GLIAL-DERIVED PRO-REPARATIVE FACTORS, AND (2) ARA-DERIVED EICOSANOIDS WHICH WILL AUGMENT CLOSURE OF INTEREPITHELIAL TIGHT JUNCTIONS WITHIN RESTITUTING EPITHELIUM. OUR SPECIFIC OBJECTIVES ARE: 1) DETERMINE THE ABILITY OF FED OLIGOSACCHARIDES TO INDUCE STRUCTURAL CHANGES IN ENTERIC MICROBIAL COMMUNITIES THAT HASTEN THE DEVELOPMENT OF THE EGC NETWORK; AND 2) DETERMINE IF SUPPLEMENTATION OF OLIGOSACCHARIDES AND ARA SYNERGISTICALLY HASTENS RECOVERY OF MUCOSAL BARRIER FUNCTION IN ISCHEMIC-INJURED NEONATAL INTESTINE BY STIMULATING EGC-REGULATED RESTITUTION AND CLOSURE OF ASSOCIATED TIGHT JUNCTIONS RESPECTIVELY. THE PROPOSED EXPERIMENTS WILL USE NOVEL PHYSIOLOGIC, CELLULAR, AND IMMUNOLABELING APPROACHES TO DEFINE DEVELOPMENT AND REPAIR OF PORCINE MUCOSA UNDER THE INFLUENCE OF TWO BIOACTIVE FOOD COMPONENTS. WE BELIEVE THE PROPOSED STUDIES WILL LEAD TO AN UNDERSTANDING OF THE MECHANISTIC CONNECTIONS BETWEEN BIOACTIVE NUTRIENTS AND GUT HEALTH.