Glucagon‐like Peptide‐2 Therapy Improves Outcomes of Intestinal Adaptation and Decreases Relative Apoptosis in a Distal Intestinal Resection Neonatal Piglet Model of Short Bowel Syndrome

Glucagon‐like peptide‐2 (GLP‐2) is an intestinotrophic hormone produced in the ileum and colon that has been shown to augment intestinal adaptation in adult short bowel syndrome (SBS). Endogenous GLP‐2 levels and intestinal adaptation are reduced in distal intestinal resection (DIR) animal models of SBS that lack remnant ileum. We hypothesize that exogenous GLP‐2 will improve clinical, morphological, and histological outcomes of intestinal adaptation in a DIR neonatal piglet model of SBS. Twelve piglets underwent a 75% DIR with a jejunocolic anastomosis. Parenteral nutrition (PN) started on day 1 and was weaned as enteral nutrition (EN) was advanced. On day 2, piglets were randomized to IV GLP‐2 (11nmol/kg/day) or saline. Comparisons were made using the Student's t‐test, and p<0.05 was considered statistically significant. GLP‐2‐ vs saline‐treated DIR piglets had fewer days of diarrhea (8.0±0.7 vs 12.3±0.4d), fewer days on PN (10.0±0.6 vs 13.8±0.2d), increased bowel length (19±4 vs −5±3%), and deeper jejunal crypts (248±21 vs 172±12μm). The fold increase in jejunal villus apoptosis was lower for DIR piglets vs surgical controls (1.1±0.1 vs 2.3±0.6 fold) in response to GLP‐2. GLP‐2 therapy improves clinical, morphological, and histological outcomes of intestinal adaptation in a DIR neonatal piglet model of SBS, and reduces relative apoptosis. These results support a potential role for GLP‐2 therapy in pediatric SBS.