Teduglutide‐Stimulated Intestinal Adaptation Is Complemented and Synergistically Enhanced by Partial Enteral Nutrition in a Neonatal Piglet Model of Short Bowel Syndrome

Background: Teduglutide, a glucagon‐like peptide‐2 (GLP‐2) analogue, is available for long‐term use by parenteral nutrition (PN)–dependent adults to promote intestinal adaptation but is not approved for use in pediatric patients. The objective of this study was to assess teduglutide‐stimulated induced intestinal adaptation, potential synergies with partial enteral nutrition (PEN), and distinct temporal markers of adaptation in a neonatal piglet model of short bowel syndrome (SBS). Materials and Methods: Neonatal piglets (48 hours old; n = 72) underwent an 80% jejunoileal resection and were randomized to 1 of 4 treatment groups, in a 2 × 2 factorial design, with PN or PEN (80% standard PN/20% standard enteral nutrition) and teduglutide (0.1 mg/kg/d) or control. Piglets received nutrient infusions for 4 hours, 48 hours, or 7 days. Results: Teduglutide improved ( P < .05) mucosal surface area (villus height: duodenum, jejunum, ileum; crypt depth: ileum, colon; proliferation: duodenum, jejunum, ileum; colon; apoptosis: jejunum, ileum, colon) and acute nutrient processing capacity (glucose: duodenum, jejunum, ileum; glutamine: duodenum, jejunum). These effects were complemented and synergistically enhanced by PEN in both site and timing of action. Structural adaptations preceded functional adaptations, but crypt depth remained a strong indicator of adaptation, regardless of time. Conclusions: The combination of teduglutide and PEN enhances intestinal adaptation beyond that of either therapy alone.