Alterations in intestinal morphology, histology and permeability with exogenous glucagon‐like peptide 2 and epidermal growth factor treatment promote intestinal adaptation in neonatal intestinal failure (137.2)

Abstract

Background: The peptide factor, glucagon‐like peptide 2 (GLP‐2), augments intestinal adaptation in adults but its efficacy in neonatal short bowel syndrome (nSBS) is not established. GLP‐2 augments the epidermal growth factor (EGF) receptor pathway, suggesting an interactive role in the maintenance of gut health.Objective: To study the efficacy of exogenous GLP‐2 and EGF administration, alone and in combination, on intestinal adaptation and function in a translational piglet model of nSBS.Methods: Neonatal piglets (aged 3‐5 days) received one of 4 treatments (saline (n=3), GLP‐2 (n=3), EGF (n=6) and GLP‐2/EGF (n=3) in combination) for 7 days following a 75% mid‐intestinal resection or no resection (sham control). Structural adaptation was assessed by morphology and histology measures. Jejunal permeability of mannitol and polyethylene glycol (PEG) was assessed using Ussing techniques. A sow‐fed control group (n=6) was also used for comparison.Results: There was no difference in body weight gain or intestinal length between groups. In the resection group, intestinal weight per length increased with EGF treatment compared to saline treatment. Jejunum villus height increased with EGF or GLP‐2 treatment but not in combination, compared to saline treatment (p<0.0001). Combination therapy decreased both jejunum crypt depth compared to saline treatment and ileum crypt depth compared to GLP‐2 or EGF treatment (p<0.001). GLP‐2 alone reduced jejunal permeability of mannitol (p=0.0007) and PEG (p=0.0054) compared to the sham‐saline group. EGF alone increased the permeability of these markers compared to GLP‐2 treatment.Conclusions: Altogether, these findings illustrate a role for GLP‐2 and EGF therapy in intestinal adaption and function but perhaps not in combination. The combination of therapies appears to dampen the adaptive response histologically. The alterations in permeability suggest an improvement in barrier function with GLP‐2 and a promotion in mucosal growth with EGF.Grant Funding Source: Supported by: CIHR, ASPEN