Gangliosides Protect Bowel in an Infant Model of Necrotizing Enterocolitis by Suppressing Proinflammatory Signals

Objectives: Necrotizing enterocolitis (NEC) has high morbidity in premature infants. Hypoxia-ischemia, infection, and enteral feeding are risk factors associated with NEC, whereas feeding human milk is protective. Vasoactive and inflammatory mediators in NEC remain elusive. Gangliosides are found in human milk and enterocyte membranes. An infant bowel model of NEC was developed to test the hypothesis that gangliosides modulate the inflammatory response to infection and hypoxia. Patients and Methods: Viable, noninflamed bowel was obtained from 9 infants between 26 and 40 weeks' gestational age. Infant bowel was treated in culture with Escherichia coli lipopolysaccharide (LPS) and hypoxia in the presence or absence of preexposure to gangliosides. Bowel necrosis and production of nitric oxide, endothelin-1, serotonin, eicosanoids, hydrogen peroxide, and proinflammatory cytokines were measured. Results: Ganglioside preexposure reduced bowel necrosis and endothelin-1 production in response to LPS. Gangliosides suppressed infant bowel production of nitric oxide, leukotriene B-4, prostaglandin E-2, hydrogen peroxide, interleukin-1 beta, interleukin-6, and interleukin-8 in response to LPS exposure and hypoxia. Conclusions: A bowel protective effect of gangliosides is indicated by modulation of vasoactive mediators and proinflammatory signal suppression. JPGN 49:382-392, 2009.