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Title: Metabolomic determinants of necrotizing enterocolitis in preterm piglets

item CALL, LEE - Children'S Nutrition Research Center (CNRC)
item STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)
item GARCIA, SELINA - Children'S Nutrition Research Center (CNRC)
item BAUCHART-THEVRET, CAROLINE - Children'S Nutrition Research Center (CNRC)
item DONNELLY, JESSICA - Children'S Nutrition Research Center (CNRC)
item SHEIKH, FARIHA - Texas Children'S Hospital
item AKINKUOTU, ADESOLA - Texas Children'S Hospital
item OLUTOYE, OLUYINKA - Texas Children'S Hospital
item WITTKE, ANJA - Mead Johnson
item Burrin, Douglas - Doug

Submitted to: Archives of Disease in Childhood
Publication Type: Abstract Only
Publication Acceptance Date: 7/29/2014
Publication Date: 10/17/2014
Citation: Call, L., Stoll, B., Garcia, S., Bauchart-Thevret, C., Donnelly, J., Sheikh, F., Akinkuotu, A., Olutoye, O.O., Wittke, A., Burrin, D.G. 2014. Metabolomic determinants of necrotizing enterocolitis in preterm piglets. Archives of Disease in Childhood. 99(Suppl 2):PO-0607b, A451.

Interpretive Summary:

Technical Abstract: Studies in premature infants and animals show that carbohydrate malabsorption and gut microbiota colonisation are key elements for triggering necrotizing enterocolitis (NEC). Our aim was to determine how dietary carbohydrate composition affects the metabolomic profile and whether unique metabolite signatures correlate with NEC incidence. Cecal contents and plasma were collected from a group of preterm pigs at birth and from three groups fed formula containing either lactose, corn syrup solids (CSS) or a 1:1 mixture of lactose:CSS (MIX) as the sole carbohydrate. We performed metabolomic analysis by LC/GC mass spectroscopy, clinical and histological NEC scoring, and distal ileum tissue expression of inflammatory markers. Results were based on clinical and histological scores NEC incidence rates were 12%, 35%, and 40% in the lactose, CSS and MIX groups, respectively. Ileum inflammatory markers (IL-8, IL-6, and IL1b) were highest in CSS vs. MIX and lactose groups and also correlated with NEC. Metabolomic analysis showed that lactose vs. CSS formula increased abundance of several cecal endocannabinoids. CSS and MIX formula increased plasma histamine, cecal and plasma lactate, beta-hydroxybutyrate, and butanediol, and decreased the abundance of several primary and secondary bile acids vs. lactose fed pigs. We concluded that lactose-based formula protects against inflammation and NEC and that this correlates with increased cecal levels of anti-inflammatory neurotransmitters and reduced levels of carbohydrate fermentation products and bile acids. This novel finding suggests that endocannabinoids, normally found in breast milk, may be produced endogenously and modulate inflammation in preterm neonates fed a lactose-based formula.