Venezia by PVII

Douglas G. Burrin, Ph.D.

Associate Professor of Pediatrics
Baylor College of Medicine
Research Physiologist, Agricultural Research Service dburrin@bcm.tmc.edu

Nutritional and Hormonal Regulation of Neonatal Gut Health and Disease

The research group has several basic and translational projects designed to establish how enteral nutrition, gut hormones, and enteric microflora function as signals to stimulate intestinal adaptation, maintain function and prevent disease in premature infants, such as necrotizing enterocolitis (NEC) and hepatic steatosis. The group has established unique models of parenteral nutrition and NEC using the neonatal piglet to address clinically-relevant problems in pediatric nutrition and gastroenterology.

Studies are aimed at establishing the cellular and physiological functions of glucagon-like peptide 2 (GLP-2), an FDA-approved gut hormone currently in clinical trial for treatment of adult short-bowel syndrome. Past studies in TPN-fed piglets were first to show the trophic and vasoactive actions of GLP-2 in the neonatal gut. More recent findings identified the cellular co-localization of the GLP-2 receptor in enteric neurons with neurotransmitters. Current studies are aimed at establishing the neurotransmitters involved in GLP-2 receptor signaling and function and prevention of NEC. The group also has shown that the gut is a key site of essential amino acid metabolism, especially methionine trans-methylation to homocysteine and transsulfuration to cysteine. Current projects in this area involving both neonatal piglets and mice are aimed at establishing the metabolic function of dietary sulfur amino acids in intestinal epithelial turnover and maintenance of redox status and health under inflammatory conditions.

Emerging projects in the lab seek to identify the cellular mechanisms and nutritional conditions, especially total parenteral nutrition (TPN), that lead to intestinal dysfunction and excessive growth of pathogenic luminal bacterial, which ultimately triggers the inflammatory response and NEC in the premature intestine. We plan to test clinically-relevant interventions that combine the beneficial actions of immunomodulatory enteral nutrition and appropriate microbial colonization to prevent NEC. Other emerging projects are designed to identify the cellular and molecular mechanism that lead to liver disease and metabolic dysfunction associated with prematurity and neonatal TPN support. Recent studies show that chronic TPN induces hepatic steatosis and insulin resistance in neonatal piglets. We will test whether this metabolic phenotype of glucose dysregulation persists beyond the neonatal period and predisposes to adolescent type 2 diabetes.

We take an integrative technical approach dictated by the research question to address relevant functions at the whole animal, tissue, cellular or molecular level. We use sophisticated metabolic, cell biological and molecular approaches, such as stable isotope metabolomics, laser-capture microdissection, in situ hybridization, gene microarray, intravital and confocal microscopic imaging to identify the cellular localization of specific signals involved in the metabolism, proliferation and survival of relevant cell types, including mucosal epithelial cells, enteric neurons, submucosal arterioles, and hepatocytes.

Representative Publications: 

Burrin, DG and B Stoll. Emerging Aspects of Gut Sulfur Amino Acid Metabolism. Curr Opin Clin Nutr Metab Care. 10:63-68, 2007.

Riedijk, MA, B Stoll, S Chako, H Schierbeek, AL Sunehag, JB van Goudoever, DG Burrin. Methionine transmethylation and transsulfuration in the piglet gastrointestinal tract. Proc Natl Acad Sci. 104:3408-3413, 2007.

Burrin, DG, B Stoll, X Guan, L Cui, X Chang. GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal piglets. Am J Physiol 292:E281-E291, 2007.

Janeczko, MJ, B. Stoll, X. Chang, X. Guan, D.G. Burrin. Extensive gut metabolism limits the intestinal absorption of excessive supplemental dietary glutamate loads in infant pigs. J. Nutr. 137:2384-2390, 2007.

Wang, H, VI Khaoustov, B Krishnan, W Cai, B Stoll, DG Burrin, B Yoffe. Total parenteral nutrition induces liver steatosis and apoptosis in newborn piglets. J Nutr. 136:2547-2552, 2006.

Stephens J, Stoll B, Cottrell J, Chang X, Helmrath M, Burrin DG. Glucagon-Like Peptide-2 Acutely Increases Proximal Small Intestinal Blood Flow in TPN-Fed Neonatal Piglets. Am. J. Physiol. 59;R283-R289, 2006.

Cottrell JJ, Stoll B, Buddington RK, Stephens JE, Cui L, Chang X, Burrin DG. Glucagon-Like Peptide-2 Protects Against TPN-induced Intestinal Hexose Malabsorption in Enterally Re-fed Piglets. Am J Physiol. 53:G293-G300, 2006.

Guan, X, HE Karpen, JT Bukowski, J Stephens, S Niu, G Zhang, B Stoll, , MJ Finegold, JJ Holst, DL Hadsell, BL Nichols, and DG Burrin. GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow. Gastroenterology. 130:150-164, 2006.

Stoll, B and DG Burrin. Measuring splanchnic amino acid metabolism in vivo using stable isotope tracers. J. Anim. Sci. 84(E. Suppl.):E60E72, 2006.

Sangild, PT, RH Siggers, M Schmidt, J Elnif, CR Bjornvad, T Thymann, ML Grondahl, AK Hansen, SK Jensen, M Boye, L Moelbak, RK Buddington, B Westrom, DG Burrin. A diet- and colonization-dependent intestinal dysfunction predisposes to necrotizing enterocolitis (NEC) in preterm pigs. Gastroenterology 130:1776-1792, 2006.

Burrin DG, Stoll B, Guan X, Cui L, Chang X, Holst JJ. Glucagon-like peptide 2 dose dependently activates intestinal cell survival and proliferation in neonatal piglets. Endocrinology. 146(1):22-32, 2005.

Niinikoski H, Stoll B, Guan X, Kansagra K, Lambert BD, Stephens J, Hartmann B, Holst JJ, Burrin DG. Onset of small intestinal atrophy is associated with reduced intestinal blood flow in TPN-fed neonatal piglets. J Nutr. 134(6):1467-1474, 2004.

Bos C, Stoll B, Fouillet H, Gaudichon C, Guan X, Grusak MA, Reeds PJ, Tome D, Burrin DG. Intestinal lysine metabolism is driven by the enteral availability of dietary lysine in piglets fed a bolus meal. Am J Physiol Endocrinol Metab. 285(6):E1246-E1257, 2003.

Kansagra K, Stoll B, Rognerud C, Niinikoski H, Ou CN, Harvey R, Burrin D. Total parenteral nutrition adversely affects gut barrier function in neonatal piglets. Am J Physiol Gastrointest Liver Physiol. 285(6):G1162-G1170, 2003.

Burrin DG, Stoll B, Chang X, Van Goudoever JB, Fujii H, Hutson SM, Reeds PJ. Parenteral nutrition results in impaired lactose digestion and hexose absorption when enteral feeding is initiated in infant pigs. Am J Clin Nutr. 78(3):461-470, 2003.

Guan X, Stoll B, Lu X, Tappenden KA, Holst JJ, Hartmann B, Burrin DG. GLP-2-mediated up regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets. Gastroenterology. 125(1):136-47, 2003.

Burrin DG, Stoll B, Guan X. Glucagon-like peptide 2 function in domestic animals. Domest Anim Endocrinol. 24(2):103-122, 2003.