Location: Children's Nutrition Research Center
Project Number: 3092-10700-070-001-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Apr 1, 2024
End Date: Mar 31, 2029
Objective:
Objective 1: Determine the immune protective function of human milk and bovine colostrum-derived IgA and protection against necrotizing enterocolitis (NEC) in a formula-fed, preterm pig model.
Sub-objective 1.A: Evaluate the effect of HM- and BC-derived sIgA on the binding and invasion of NEC-associated bacteria to the human intestinal epithelium in vitro.
Sub-objective 1.B: Investigate the contribution of HM- and BC- derived sIgA supplementation to modify the gut microbiome and protect against NEC in preterm piglets.
Objective 2: Determine the impact of citrulline and arginine supplementation on metabolism and prevention of necrotizing enterocolitis (NEC) incidence in formula-fed preterm pigs.
Sub-objective 2.A: Determine the impact of citrulline and arginine supplementation on the prevention of NEC and organ and systemic levels of arginine, citrulline, and nitrous oxide in preterm neonatal piglets.
Sub-objective 2.B: Identify the mechanisms by which citrulline and arginine maintain barrier function and reduce inflammation in the gastrointestinal tract.
Objective 3: Determine the nutritional regulation of muscle growth following preterm birth and develop targeted amino acid supplementation to promote lean growth and optimal development.
Sub-objective 3.A: Determine the nutritional regulation of muscle growth following preterm birth.
Sub-objective 3.B: Develop targeted amino acid supplementation to promote lean growth and optimal development following preterm birth.
Objective 4: Determine the optimum bioavailability of different chemical forms of choline that maximize the plasma and tissue deposition and function of long chain fatty acids in preterm pigs.
Sub-objective 4.A: Determine the enrichment of choline in the liver, lung, and brain in preterm pigs of choline by administration of choline metabolites found in human milk.
Sub-objective 4.B: Determine which form of choline in conjunction with DHA and ARA will provide the greatest enrichment of DHA and ARA in the brain in premature pigs.
Approach:
Despite advances in medical care, many infants in the U.S. are born prematurely, with low birth weight and increased risk of poor growth, development, and disease. Necrotizing enterocolitis (NEC), a leading cause of death in the preterm, has been linked to the feeding of infant formula compared to human milk and to poor gastrointestinal perfusion. We seek to identify the mechanisms that regulate the diminished growth and altered metabolic responses to nutrition in premature infants and develop new strategies to optimize their growth/development and prevent disease. We will use neonatal piglet models to determine the extent to which the anabolic resistance to nutrition contributes to reduced muscle growth in the preterm and whether targeted amino acid supplementation will promote lean growth. We will determine the immune protective function of human milk and bovine colostrum-derived immunoglobulin A (IgA) and protection against NEC in the preterm. This project will ascertain the impact of citrulline and arginine supplementation on metabolism and prevention of NEC in the preterm. We will determine the optimum bioavailability of different chemical forms of choline that maximize the plasma and tissue deposition and function of long chain fatty acids in the preterm. This project is expected to provide novel information that will be directly useful in optimizing the nutritional management of premature and low birth weight infants and improve their long-term metabolic health and growth.
