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Gangliosides protect bowel in an infant model of necrotizing enterocolitis by suppressing pro‐inflammatory signals of infection and hypoxia
Author(s) -
Schnabl Kareena Leanne,
Larsen Bodil,
Van Aerde John E,
Lees Gordon,
Evans Mark,
Clandinin Michael Thomas
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a738-a
Subject(s) - necrotizing enterocolitis , medicine , inflammatory bowel disease , hypoxia (environmental) , nitric oxide , lipopolysaccharide , immunology , proinflammatory cytokine , vasoactive intestinal peptide , inflammation , gastroenterology , chemistry , disease , organic chemistry , oxygen , receptor , neuropeptide
Necrotizing enterocolitis (NEC) is an inflammatory bowel disease of neonates with high morbidity in premature infants. Hypoxia‐ischemia, infection and enteral feeding are risk factors while feeding human milk is protective. The role of vasoactive and inflammatory mediators in NEC remains elusive due to limitations in models. An infant bowel model of NEC was developed to test the hypothesis that gangliosides, human milk glycolipids with anti‐inflammatory properties, modulate the inflammatory response of infant bowel to infection and hypoxia. Viable, non‐inflamed infant bowel was obtained from 0–3 month infants requiring bowel surgery. Cultured infant bowel was treated with E. coli lipopolysaccharide (LPS) and hypoxia in the presence and absence of gangliosides. Bowel necrosis and production of nitric oxide, endothelin‐1, eicosanoids, hydrogen peroxide and pro‐inflammatory cytokines were measured. Gangliosides reduced bowel necrosis in response to E. coli LPS. Gangliosides also suppressed bowel production of nitric oxide, endothelin‐1, LTB 4 , PGE 2 , H 2 O 2, IL‐1β, IL‐6 and IL‐8 in response to E. coli LPS and hypoxia. These findings indicate a bowel protective effect of gangliosides through pro‐inflammatory signal suppression, modulation of vasoactive mediators and anti‐oxidant effects. The results provide a strong rationale for ganglioside use in food products to treat inflammatory bowel diseases. This research project was funded by the Canadian Institute of Health and the Natural Sciences and Engineering Research Council.