| Premature and low birth weight infants frequently have increased metabolic requirements and developmentally immature gastrointestinal function and are supported totally or partially on parenteral nutrition for several days to weeks postpartum. The use of total parenteral nutrition (TPN) is frequently associated with a myriad of complications, primarily due to the lack of enteral stimulation. In neonates, TPN reduces gastrointestinal hormone secretion, compromises intestinal morphology and disaccharidase activity and alters systemic immune function. The impact of TPN on intestinal immune cell composition in neonates has been poorly characterized. Therefore, the central objective of this doctoral research was to determine the effects of TPN on intestinal immune cell composition in the developing intestine. The neonatal piglet was used as the model for the human infant. In experiment 1, piglets receiving TPN for seven days demonstrated compromised intestinal morphology and a greater number of intestinal CD4+ and CD8+ T-lymphocytes, goblet cells, and mast cells. An inverse correlation between T-lymphocyte numbers and intestinal morphology was observed (r > --0.80; P < 0.05), suggesting an association between TPN-induced gut atrophy and intestinal T-lymphocyte expansion. Partial enteral nutrition (PEN) is used in the clinical setting to avoid complications of TPN and promote GI development. Provision of 20% of energy as PEN to neonatal pigs receiving parenteral nutrition improved intestinal morphology and enzyme activities. In experiment 2, the provision of 20% of total calories enterally (PEN) ameliorated TPN-induced alterations in intestinal immune cell composition after 7 days. Experiment 3 was designed to ascertain the temporal relationship between TPN-induced changes in intestinal structure, function and immune cell composition. Significant alterations in intestinal morphology, enterocyte migration, barrier-function, disaccharidase activity, sodium-dependent glucose transport, and immune cellularity were evident after 2 days of TPN, and persisted at one week of TPN. T-lymphocyte numbers was significantly correlated with tissue conductance, further supporting an association between intestinal immune cell composition, villus architecture and barrier function. These data illustrate the acute sensitivity of intestinal immune cell composition to enteral nutrient stimulation, support early initiation of PEN in neonates on TPN, and creates a framework for the elucidation of mechanisms underlying TPN-induced gut atrophy. |
