This program project renewal application is submitted by investigators who proposed to expand and continue their studies of the unique properties of human milk. The seven component subprojects address through in vivo protocols the biologic consequences of specific milk components or properties that the investigators have studied primarily in vitro during the initial funding period. In general, the subprojects seek to characterize the biologic interaction of milk components or properties at the interface of the milk with the GI lumen. Certain consequences of the luminal milk - GI tract interaction that pertain to the well-being of the infant also will be examined. When appropriate, human infants will be studied as subjects. Other neonatal mammals are utilized when human subjects are not appropriate for the protocol. In respective subprojects, we propose to consider: (1) whether lymphocytes and macrophages in human colostrum mediate protection to neonatal subjects via transfer of maternal cellular immunity and provision of accessory cell function, respectively; (2) the protective effect of milk in vivo against viral infections and (3) against Escherichia coli and Clostridium difficile diarrhea; (4) the pharmacokinetics of three new broad spectrum cephalosporin antibiotics administered to the lactating woman and the clinical significance for her nursing infant; (5) using stable isotope methods, the net absorption and balance of calcium, iron, and zinc in preterm infants fed human milk or formula and the effects of increasing postnatal age or milk fortification with these specific mineral nutrients; (6) the unique effects of postpartum age-specific milk on GI growth, motility, and intestinal and pancreatic functions; and (7) the protective effects of milk phospholipids on GI tract integrity as part of a continuum with amniotic fluid in the prevention of necrotizing enterocolitis.
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