INTESTINAL PERMEABILITY TO SMALL-MOLECULAR-WEIGHT AND LARGE-MOLECULAR-WEIGHT SUBSTANCES IN THE NEWBORN RABBIT

Background/Purpose: The authors have previously reported the occurrenc e of spontaneous bacterial translocation (BT) and its resolution with age in the newborn rabbit. They have also reported a close correlation between small bowel bacterial colonization (BC-SB) and BT at 1 week o f age, suggesting that the presence of luminal bacteria and their prod uction of endotoxins may increase the intestinal permeability. The aim of this study was to evaluate intestinal permeability to small and la rge molecules in the newborn rabbit and to correlate it with BT Materi als and Methods: New Zealand White rabbits (n = 96) 1, 7, 14, 21, and over 120 days (adult) of age were given either C-14-labeled ethylene d iamine tetraacetic acid (EDTA) (MW 290) or C-14-Dextran (MW 70,000) vi a an orogastric tube at 1 mCi per 100 g of body weight. Five hours lat er, blood, urine, liver, and intestine were collected, and scintillati on counting was performed after solubilization. In a separate series o f rabbits (n = 136), the incidence of BT BC-SB, and small intestinal s urface area (SA) were measured. Results: Total permeability to Dextran decreased with age and was significantly reduced at 14 days of age. I n contrast, total permeability to EDTA increased and was maximal in 7- to 14-day-old rabbits and began to decrease at 21 days of age. The inc idence of BC-SB rapidly increased at 7 days of age and reached 100% at 14 days of age. The incidence of BT peaked at 7 days of life (30%) an d then decreased with age. SA increased rapidly in the first 3 weeks a nd SA growth rate of 21-day-old rabbits was almost 1,400% compared wit h 1-day old rabbits. Conclusions: This study has shown an age-related reduction of intestinal permeability to large (Dextran) and small (EDT A) molecular weight particles. However, intestinal permeability to EDT A had a different pattern than Dextran, suggesting that there may be d ifferent mechanisms of intestinal permeability to different size molec ules. Intestinal permeability to EDTA closely correlated with bacteria l colonization and bacterial translocation, suggesting that changes in the intestinal bacterial environment may affect the intestinal permea bility, possibly by activating the immune system secondary to increase s in endotoxins and bacteria. Copyright (C) 1997 by W.B. Saunders Comp any.