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.

The mixed lipid, having less ω-6 PUFA and more ω-3 PUFA, was able to prevent liver disease and reduce systemic inflammation in PN-fed neonatal piglets. However, this lipid did not increase plasma or brain DHA status, which would be desirable for neonatal developmental outcomes.

BackgroundGlucagon‐like peptide‐2 (GLP‐2) is an intestinotrophic factor released from L‐cells in the ileum, a segment commonly resected or atretic in neonatal short bowel syndrome (SBS). In piglets, ileal resection decreases intestinal adaptation and endogenous GLP‐2 production, whereas exogenous replacement promotes adaptation. In this study, we determined the effect of a novel long‐acting GLP‐2 analogue, FE 203799 (FE; apraglutide), upon intestinal growth, adaptation, and function in neonatal SBS piglets without ileum.MethodsNeonatal piglets were randomized to saline (n = 10) vs FE treatment (n = 8). All piglets underwent 75% intestinal resection with jejunocolic anastomosis and were pair‐fed parenteral and enteral nutrition. Saline and FE (5 mg/kg) treatments were administered subcutaneously on days 0 and 4. On day 6, 24‐hour fecal samples were collected for subsequent nutrient analysis. On day 7, small‐intestinal length and weight were measured and tissue collected for analyses.ResultsOn day 7, saline and FE‐treated piglets were healthy and gained equivalent weight (P = 0.12). Compared with saline piglets, FE‐treated piglets had lower fecal fat (P = 0.043) and energy (P = 0.043) losses and exhibited intestinal lengthening (P = 0.001), greater small‐intestinal weight (P = 0.004), longer villus height (P = 0.027), and greater crypt depth (P = 0.054).ConclusionsThe subcutaneous GLP‐2 analogue, FE, enhanced intestinal adaptation in a neonatal model of SBS without ileum. The observed intestinal lengthening with FE treatment was unique compared with our prior experience with native GLP‐2 in this same model and has important clinical implications for treating neonatal SBS. At this developmental stage, growth in the intestine, if augmented, could accelerate weaning from parenteral nutrition.

GLP-2 therapy improves clinical, morphological, and histological outcomes of intestinal adaptation in a distal-intestinal resection model of SBS. Since this anatomical subtype represents the majority of clinical cases of neonatal SBS, these results support a potential role for GLP-2 therapy in pediatric SBS.

The exogenous administration of GLP-2 is associated with the improvement of cholestasis and liver injury. This study introduces a novel role for GLP-2 in improving PNALD in the setting of prolonged PN duration.