Objectives: Necrotizing enterocolitis (NEC) is complex disease thought to occur as a result of an immaturity of the gastrointestinal tract of preterm infants. Intestinal dysfunction induced by total parental nutrition (TPN) may increase the risk for NEC upon introduction of enteral feeding. We hypothesized that the intestinal trophic and anti-inflammatory actions previously ascribed to the gut hormone, glucagon-like peptide-2 (GLP-2), would reduce the incidence of NEC when given in combination with TPN in preterm piglets.
Methods: Preterm, newborn piglets were nourished by TPN and infused continuously with either human GLP-2 (100 μg · kg−1 · day−1) or control saline for 2 days (n = 12/group). On day 3, TPN was discontinued and pigs were given orogastric formula feeding every 3 hours, and continued GLP-2 or control treatment until the onset of clinical signs of NEC for an additional 96 hours and tissue was collected for molecular and histological endpoints.
Results: GLP-2 treatment delayed the onset of NEC but was unable to prevent a high NEC incidence (∼70%) and severity that occurred in both groups. GLP-2–treated pigs had less histological injury and increased proximal intestinal weight and mucosal villus height, but not crypt depth or Ki-67–positive cells. Inflammatory markers of intestinal myeloperoxidase were unchanged and serum amyloid A levels were higher in GLP-2–treated pigs.
Conclusions: GLP-2 did not prevent NEC and a proinflammatory response despite some reduction in mucosal injury and increased trophic effect.
*USDA/ARS Children's Nutrition Research Center, the Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Houston
†Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX
‡Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Address correspondence and reprint requests to Dr Douglas G. Burrin, Children's Nutrition Research Center, 1100 Bates Street, Houston, TX 77030 (e-mail: firstname.lastname@example.org).
Received 14 September, 2012
Accepted 7 January, 2013
This work was supported by federal funds from the US Department of Agriculture, Agricultural Research Service under Cooperative Agreement Number 58-6250-6-001, and the Texas Medical Center Digestive Diseases Center (NIH Grant P30 DK-56338). The contents of this publication do not necessarily reflect the views or policies of the US Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.
The authors report no conflicts of interest.