Grant: Operating Grant

Short bowel syndrome (SBS) occurs after loss of a large part of the small intestine, which absorbs food. This occurs often in premature babies, due to diseases that start during pregnancy or after birth, and require surgery. The remaining intestine is not able to absorb nutrition for the babies to survive and grow. More than one third of the babies die from complications, mainly of the intravenous nutrition they must have to live and grow. SBS is the most common cause for small intestine transplantation in Canada, although half of these young children die waiting for a transplant, due to a lack of donors. We need better solutions for babies with SBS, who are unable to improve their intestinal absorption over time (called adaptation), to avoid their early death or need for transplantation. Otherwise, 1% of all children aged less than four years may die from this condition. Based on our research to date, we believe a hormone called glucagon like peptide-2 (GLP-2) is a potential solution. This hormone helps the intestine to grow in newborn babies and is produced in a part of the intestine called the ileum, which is the part most often surgically removed in babies with SBS. We want to study GLP-2 treatment and adaptation in piglets, a recognized animal model for small babies with SBS. We believe that GLP-2 treatment will increase adaptation in SBS piglets; especially if it is given early after surgery and if they don't have ileum. By studying piglets we can learn more about how GLP-2 works to help the intestine grow and adapt then could be learnt from studies in babies, without multiple invasive procedures to collect intestinal tissue. We will study SBS piglets, measuring growth and adaptation, with and without GLP-2 treatment. At the same time we will also study a new way to measure adaptation (measuring arginine, an amino acid made in the intestine of babies and piglets) so that we can do better studies in babies in the future, without needing to collect tissues.