Email

doug.burrin@usda.gov

Positions

Research Physiologist

USDA-ARS
Children's Nutrition Research Center

Professor Pediatrics

Baylor College of Medicine
Houston, TX US

Director, Fellowship Research Training,

Pediatric Nutrition and Gastroenterology

Education

Post-Doctoral Fellowship at Baylor College Of Medicine

Houston, TX United States

PhD from University Of Nebraska

Lincoln, Nebraska United States

MS from University Of Nebraska

Lincoln, Nebraska United States

BS from Purdue University

West Lafayette, Indiana United States

Professional Statement

Our laboratory works on basic and translational projects designed to establish how nutritional support, enteral versus parenteral, effects gut and liver function and susceptibility to disease in early development. We use the neonatal piglet in unique models of parenteral nutrition-associated liver disease (PNALD), necrotizing enterocolitis (NEC) to address clinically-relevant problems in pediatric gastroenterology.

Current projects in the laboratory seek to identify the cellular and molecular mechanism that lead to PNALD and metabolic dysfunction associated with prematurity and neonatal parenteral nutrition (PN) support. Our recent studies show that chronic PN induces hepatic steatosis, cholestasis and insulin resistance in both term and premature neonatal piglets. We are exploring how nutrients affect inter-organ and local cellular signaling pathways involved in hepatic lipid metabolism and bile acid homeostasis. We are currently exploring how specific nutrients in commercial lipid emulsions (Intralipid, Omegaven, SMOF) alter the susceptibility to PNALD. Our work shows that the new generation fish oil-based lipid emulsions markedly reduce the incidence of cholestatic liver injury and steatosis compared to Intralipid. We recently showed that secretion of a key enterokine, fibroblast growth factor 19 (FGF19), involved in bile acid homeostasis is markedly reduced under conditions of TPN. We showed that minimal enteral bile acid feeding restores FGF19 secretion and prevents cholestasis in TPN fed piglets. We have also recently demonstrated that intermittent, bolus enteral feeds are superior to continuous feeding in terms of preventing hepatic steatosis and glucose intolerance in neonatal piglets. We are also testing whether the adverse metabolic phenotype induced by PN is programmed and persists beyond the neonatal period and predisposes to adolescent fatty liver disease and type 2 diabetes.

Additional studies are using a clinically relevant, premature piglet model of NEC to establish the critical elements of pathogenesis and strategies for prevention. Our previous studies using this model established that prematurity and microbial colonization are necessary elements in the pathogenesis of NEC. More recently we have shown that TPN support prior to introduction of formula feeding increases the incidence of NEC. We also demonstrated that malabsorption of carbohydrates, namely maltodextrins, in infant formula can trigger bacterial overgrowth and promote the onset of NEC. Current studies are aimed at establishing how dietary carbohydrate shapes the microbiome-metabolomic interaction with the host immune function and prevents NEC.

Projects in the laboratory also are aimed at establishing the cellular and physiological functions of glucagon-like peptide 2 (GLP-2), an FDA-approved gut hormone for treatment of adult short-bowel syndrome. Our previous studies in TPN-fed piglets were first to show the trophic and vasoactive actions of GLP-2 in the neonatal gut. We identified the cellular co-localization of the GLP-2 receptor in enteric neurons with neurotransmitters. Current studies are aimed at establishing unique enteral approaches that trigger enteroendocrine cell TGR5-receptor-mediated signaling mechanisms of GLP-2 secretion and GLP-2 receptor function. We are testing the efficacy of GLP-2 administration and enteral GLP-2 secretagogues for treatment of SBS in neonatal piglet models.

Our research projects take an integrative experimental approach dictated by the scientific or clinical 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 micro-dissection, gene microarray, and confocal microscopic imaging to identify the cellular localization of specific signals involved in the metabolism, proliferation and survival of relevant cell types, including gut enteroids, mucosal epithelial cells and hepatocytes.

Websites

Selected Publications

• Robinson JL, Smith VA, Stoll B, Agarwal U, Premkumar MH, Lau P, Cruz SM, Manjarin R, Olutoye OO, Burrin DG, Marini JC "Prematurity reduces citrulline-arginine-nitric oxide production and precedes the onset of necrotizing enterocolitis in piglets." 2018; Pubmed PMID: 30048597
• Call L, Stoll B, Oosterloo B, Ajami N, Sheikh F, Wittke A, Waworuntu R, Berg B, Petrosino J, Olutoye O, Burrin D. "Metabolomic signatures distinguish the impact of formula carbohydrates on disease outcome in a preterm piglet model of NEC." 2018 Jun;6(1):111.
• Guthrie G, Premkumar M, Burrin DG "Emerging Clinical Benefits of New-Generation Fat Emulsions in Preterm Neonates." 2017;32:326-336.
• "Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome: translational relevance and challenges." ; Pubmed PMID: 25342047