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Exogenous glucagon-like peptide 2 and epidermal growth factor are important trophic factors associated with enhanced intestinal tissue repair and barrier function in a piglet model of intestinal failure
The digestive tract of newly weaned pigs undergoes rapid and substantial adaptation to multiple stressors, as such, specific ingredients are included in early diets to aid in gut adaptation and promote gut health. Recent cautionary use of blood and intestinal products in early weaned pig diets has emphasized the need to understand what factors may play an important role in intestinal adaptation. This study assessed the efficacy of 2 gut trophic factors (exogenous GLP-2 and EGF, alone and in combination) on ileal gut adaptation using a piglet model of intestinal failure. Neonatal piglets (age 3-5 days) received one of 4 treatments [saline (n=7), GLP-2 (n=5), EGF (n=4) and GLP-2+EGF (n=6)] for 7 days after surgical modification (75% mid-intestinal resection). Pigs were fitted with venous and gastric catheters and daily nutrient supply was provided using a combination of parenteral (80% of daily nutrient requirements) and enteral (20% of daily nutrient requirements) nutrition. The GLP-2 and EGF were provided in the parenteral and enteral solutions, respectively. Expression of genes related to tissue repair (trefoil factor 3, TTF3), cell proliferation (ki-67), differentiation (cdx2), and apoptosis (caspase 3), digestive enzymes (intestinal alkaline phosphatase, IAP), and tight junction proteins (claudin 7 and 15) were assessed. Statistical analysis was completed using a two-way ANOVA. Expression of TFF3 increased 2.7, 2.5, and 2.5 fold (P<0.01) in pigs provided GLP-2, EGF, or the combination, respectively. The combination therapy tended to increase (P=0.09) IAP expression 1.7-fold. GLP-2 and EGF alone tended to increase (P<0.07) claudin-7 expression 1.4-fold but GLP-2 and the combination increased (P<0.05) claudin-15 expression 2.7- and 2.4-fold, respectively. There was no effect of treatment on expression of ki-67, cdx2, or c3. Intestinal adaptation with exogenous GLP-2 and EGF therapy is enhanced through mechanisms of tissue repair, as well as, digestive and barrier function rather than cell proliferation or apoptosis. The combination therapy provided little additional benefit.
Keywords: intestinal adaptation, piglets, trophic factors