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Research Project: Molecular, Cellular, and Regulatory Aspects of Nutrition During Development

Location: Children's Nutrition Research Center

Title: Microbial and metabolic signatures of necrotizing enterocolitis in formula-fed piglets

item CALL, LEE - Children'S Nutrition Research Center (CNRC)
item STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)
item OLUTOYE, OLUYINKA - Baylor College Of Medicine
item AJAMI, NADIM - Baylor College Of Medicine
item PETROSINO, JOSEPH - Baylor College Of Medicine
item WITTKE, ANJA - Baylor College Of Medicine
item WAWORUNTU, ROSALINE - University Of Illinois
item BERG, BRIAN - University Of Illinois
item Burrin, Douglas - Doug

Submitted to: Pediatric Academic Society
Publication Type: Abstract Only
Publication Acceptance Date: 3/23/2016
Publication Date: 4/30/2016
Citation: Call, L., Stoll, B., Olutoye, O., Ajami, N., Petrosino, J., Wittke, A., Waworuntu, R., Berg, B., Burrin, D. 2016. Microbial and metabolic signatures of necrotizing enterocolitis in formula-fed piglets [abstract]. The Pediatric Academic Society Annual Conference, Session: Platform: Pediatric Nutrition, E-PAS2016:3140.2. April 30–May 3, 2016, Baltimore, Maryland. Available:

Interpretive Summary:

Technical Abstract: Major risk factors for necrotizing enterocolitis (NEC) include premature birth, formula feeding, and microbial colonization of the gastrointestinal tract. We previously showed that feeding formula composed of lactose vs corn syrup solids protects against NEC in preterm pigs, however the microbial and metabolic effects of different formula carbohydrates has not been explored in detail. Our objective was to characterize the effects of lactose- and corn syrup solids-based formulas on the metabolic and microbial profiles of preterm piglets and to determine whether unique metabolomic or microbiome signatures correlate with severity or incidence of NEC. The design used was that preterm piglets (103d gestation) were given total parenteral nutrition for 2d followed by enteral formula feeding from 3-7d. Pigs were fed formulas matched in nutrient content but containing either lactose (LAC), corn syrup solids (CSS) or 1:1 mix (MIX). Cecal contents and plasma were analyzed by LC/GC mass spectroscopy. Gut contents and mucosal samples were collected for DNA and RNA isolation. The V4 region of the 16S rRNA gene was sequenced, and bacterial load was measured by qPCR. Restults of NEC incidence was 14%, 42%, and 45% in the LAC, MIX, and CSS groups, respectively. Ileum inflammatory markers (IL-8, IL-6, and IL1b) were highest in CSS vs MIX and LAC groups and also correlated with NEC. TCA cycle intermediates were increased in the plasma of CSS and MIX vs LAC pigs; bile acids were decreased. Markers of glycolysis (lactate, pyruvate) were increased in the cecal contents of CSS vs LAC pigs and in plasma of NEC pigs. The dominant classes of bacteria were bacilli, clostridia, and gammaproteobacteria. NEC vs healthy phenotype and CSS vs LAC formula both showed decreased bacterial diversity. The abundance of Clostridium was increased, whereas that of Escherichia-Shigella was decreased in CSS vs LAC and NEC vs healthy pigs. Bacterial load was not different between either the diet groups or healthy vs NEC groups. We concluded that lactose-based formula protects against inflammation and NEC and that this correlates with key changes in energy, glucose, and bile acid metabolism. Feeding formula containing lactose vs corn syrup solids selects for greater microbiota diversity and is associated with decreased Clostridium and lower NEC incidence.