Grant: Project Grant

Human milk promotes intestinal growth, immune modulation and a healthy microbial environment. These benefits are particularly important for premature infants. Deficiencies in intestinal integrity, barrier function, digestive capacity and intestinal immune function lead to an increased susceptibility to gastrointestinal inflammatory diseases, such as necrotizing enterocolitis (NEC). We are applying systems biology approaches to better understand the mechanism by which human milk promotes the maturation of the gastrointestinal tract (GIT) and the associated immune system. Given emerging evidence that milk contains microRNAs in vesicles that remain active upon ingestion by infants for delivery to intestinal cells, we posit that these human milk microRNAs play a role in GIT regulation of the immune response in preterm infants. Human milk vesicles will be prepared from milk-donor women and analyzed for microRNA content and their biological anti-inflammatory activity on intestinal cell models and validated in organ culture of the immature human intestine and a mouse NEC model. These studies will provide a proof of concept establishing a role for milk microRNAs in the regulation of intestinal function.