Novel Neonatal Piglet Models of Surgical Short Bowel Syndrome With Intestinal Failure

Abstract

Short bowel syndrome occurring after surgery for acquired or congenital intestinal abnormalities causes considerable neonatal morbidity and mortality. Animal models are a valuable research tool for this problem; however, few successful neonatal models have been developed and most do not include distal intestinal resection as seen commonly in human babies. We report novel piglet models addressing these gaps. Neonatal piglets (1-6 days) underwent venous and gastric catheter insertion and 75% intestinal resection. Group 1 (n = 6) had midintestinal resection with jejunoileal anastomosis; group 2 (n = 5) had distal intestinal resection with jejunocolic anastomosis; group 3 (n = 5) were sham controls; and group 4 (n = 5) were sow reared. Postoperatively, groups 1 to 3 piglets commenced parenteral nutrition (PN), and enteral nutrition was introduced and advanced using a standard regimen. Data collection included days on PN, weight gain, fat absorption, small intestine lengthening, and bowel/liver histology. Group 2 piglets had more days on PN (P = 0.008), less weight gain (P = 0.027), and greater malabsorption (P = 0.012). They did not show small intestine lengthening and had more cholestatic liver disease. Group 1 piglets had histological evident intestinal adaptation and 1.5-fold intestinal lengthening (P = 0.001). These novel piglet models of short bowel syndrome are the first to represent the full clinical spectrum of intestinal failure as observed in human neonates. By considering the impact of different short bowel anatomy on potential for adaptation and growth, these animal models are a significant advance. They permit evaluation of new therapies to promote intestinal adaptation and reduce complications, such as cholestasis.