Omega-3 polyunsaturated fatty acids and the eicosapentaenoic acid metabolite 18-hydroxyeicosapentaenoic acid (18-HEPE) attenuate experimental necrotizing enterocolitis.

Necrotizing enterocolitis (NEC), a devastating gastrointestinal disease in infants born prematurely, is linked to intestinal inflammation. Maternal intake of omega-3 polyunsaturated fatty acids (PUFAs) has been reported as protective against inflammatory reactions in their offspring. We hypothesized that omega-3 fatty acids would prevent intestinal injury in an experimental model of NEC. Elevated omega-3 levels in mouse pups were achieved either by enriching dam-fed diets with omega-3 or by endogenous production in transgenic fat-1 mice able to convert omega-6 to omega-3. Mucosal injury scores decreased in pups of dams fed fish oil, compared to those fed safflower oil. Pro-inflammatory cytokines IL6 and TNFα were lower in pups of mothers fed fish oil, compared to those fed safflower oil. Comparable results were obtained in fat-1 transgenic pups. Elevated levels of 18-hydroxyeicosapentaenoic acid (18-HEPE) were detected in the distal ilea of pups in both models, suggesting that this eicosapentaenoic acid metabolite could mediate the observed protection. In the absence of maternal omega-3 supplementation, exogenous administration of 18-HEPE in wild-type pups, protected against intestinal injury. Maternal omega-3 supplementation prevented NEC and 18-HEPE could serve as a candidate novel therapy for either the prevention or treatment of neonatal intestinal injury.