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- W2023289719 abstract "Background: Necrotizing enterocolitis is an inflammatory bowel disease of neonates and remains the leading gastrointestinal emergency in premature infants due to inadequate treatments. The underlying pathogenic mechanisms remain elusive but prematurity, infection, ischemia-hypoxia and enteral feeding are established risk factors while breastfeeding is protective. The role of local vasoactive and inflammatory mediators in the underlying pathogenesis of necrotizing enterocolitis is unclear due to limitations in current models. A human model representative of necrotizing enterocolitis does not exist. The objective of this study is to develop a human neonatal bowel model that is more representative of necrotizing enterocolitis and to determine whether gangliosides, human milk glycolipids with microbial and anti-inflammatory properties, reduce necrosis and pro-inflammatory signals in human neonatal bowel exposed to E. coli lipopolysaccharide and hypoxia. Methods: Immunohistochemistry was used to access viability of full thickness bowel specimens from 0-3 month-old infants undergoing intestinal surgery. In culture, neonatal bowel was treated with E. coli lipopolysaccharide and hypoxia in the presence and absence of a ganglioside pre-exposure. Bowel necrosis and production of nitric oxide, serotonin, eicosanoids and pro-inflammatory cytokines was measured. Results: Analysis of hematoxylin/eosin stained neonatal bowel revealed viable tissue with intact villi and no infiltration of immune cells. Gangliosides reduced bowel necrosis triggered by E. coli lipopolysaccharide. We demonstrate that gangliosides reduce lipopolysaccharide- and hypoxia-induced bowel production of nitric oxide, LTB4, IL-1β, IL-6 and IL-8. Conclusions: A human neonatal bowel model that incorporates multiple risk factors for necrotizing enterocolitis was developed to investigate further the pathogenesis and treatment for necrotizing enterocolitis. These findings show that gangliosides improve neonatal bowel survival by down-regulating pro-inflammatory signals released by neonatal bowel during infection and hypoxia." @default.
- W2023289719 created "2016-06-24" @default.
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- W2023289719 date "2006-11-01" @default.
- W2023289719 modified "2023-09-25" @default.
- W2023289719 title "Gangliosides Improve Human Neonatal Bowel Survival in Necrotizing Enterocolitis by Suppressing Inflammatory Signals During Infection and Hypoxia" @default.
- W2023289719 doi "https://doi.org/10.1097/01.mpg.0000256265.60986.1a" @default.
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