The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine

• Published in: British journal of nutrition Vol. 116; no. 7; pp. 1175 - 1187
• Main Authors: Good, Misty, Sodhi, Chhinder P., Yamaguchi, Yukihiro, Jia, Hongpeng, Lu, Peng, Fulton, William B., Martin, Laura Y., Prindle, Thomas, Nino, Diego F., Zhou, Qinjie, Ma, Congrong, Ozolek, John A., Buck, Rachael H., Goehring, Karen C., Hackam, David J.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 14-10-2016
• Subjects: Animals; Animals, Newborn; Breast milk; Breastfeeding & lactation; Digestive system; Disease Models, Animal; Enterocolitis, Necrotizing - physiopathology; Enterocolitis, Necrotizing - prevention & control; Female; Gangrene; Gene Expression - drug effects; Humans; Infant, Newborn; Infant, Premature, Diseases - physiopathology; Intestinal Mucosa - blood supply; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiota - drug effects; Milk, Human - chemistry; Nitric oxide; Nitric Oxide - analysis; Nitric Oxide Synthase Type III - deficiency; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - physiology; Nutritional Immunology; Premature birth; Splanchnic Circulation - drug effects; Trisaccharides - administration & dosage; Endothelial nitric oxide synthase; Necrotising enterocolitis; Human milk oligosaccharides; 2′-Fucosyllactose; Breast milk; HMO human milk oligosaccharide; 2′FL 2′-fucosyllactose; LPS lipopolysaccharide; eNOS endothelial nitric oxide synthase; TLR4 toll-like receptor 4; NEC necrotising enterocolitis
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114516002944

Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2′-fucosyllactose (2′FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2′FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2′FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2′FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2′FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2′FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2′FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC.