Combined Glucagon‐like Peptide‐2 and Epidermal Growth Factor Therapy Maximally Stimulates Adaptation in Neonatal Intestinal Failure without Ileum

Abstract

PurposeMost infants with intestinal failure (IF) suffer from loss of distal intestine, and ileum. We studied the effect of glucagon‐like peptide‐2 (GLP2) and epidermal growth factor (EGF) therapy in a novel preclinical IF model with distal resection.MethodsNeonatal piglets received one of 4 treatments (saline, GLP2, EGF, or GLP2/EGF in combination; n=6 in all groups) for 7 days after a 75% distal intestinal resection or no resection (sham). Adaptation was assessed by gut morphology, histology and permeability to mannitol. qRT‐PCR was performed for insulin‐like growth factor‐1 (Igf1), its receptor (Igf1r) and Egfr. Data are analyzed by two‐way ANOVA.ResultsCombination therapy increased intestinal length and mucosal weight over GLP2 or EGF alone and saline (p<0.01). Villus height increased with GLP2 but increased most with combination therapy compared to saline (p<0.01). Combination therapy decreased intestinal permeability to mannitol over GLP2 or EGF alone and saline (p<0.01). Igf1r expression increased with EGF and decreased with GLP2, with no effect on Igf1 or Egfr (p=0.03).ConclusionsThe adaptive changes present a role for combined GLP2 and EGF therapy in neonatal IF without ileum. Unlike mid‐intestinal resection, the effects of GLP2 or EGF alone are not as pronounced, nor is Igf1 upregulated, highlighting remnant anatomy as an important determinant of treatment effects.