title: Necrotizing enterocolitis: new insights into pathogenesis and mechanisms.
abstract: Necrotizing enterocolitis (NEC) is the most frequent and lethal disease of the gastrointestinal tract of preterm infants. At present, NEC is thought to develop in the premature host in the setting of bacterial colonization, often after administration of non-breast milk feeds, and disease onset is thought to be due in part to a baseline increased reactivity of the premature intestinal mucosa to microbial ligands as compared with the full-term intestinal mucosa. The increased reactivity leads to mucosal destruction and impaired mesenteric perfusion and partly reflects an increased expression of the bacterial receptor Toll-like receptor 4 (TLR4) in the premature gut, as well as other factors that predispose the intestine to a hyper-reactive state in response to colonizing microorganisms. The increased expression of TLR4 in the premature gut reflects a surprising role for this molecule in the regulation of normal intestinal development through its effects on the Notch signalling pathway. This Review will examine the current approach to the diagnosis and treatment of NEC, provide an overview of our current knowledge regarding its molecular underpinnings and highlight advances made within the past decade towards the development of specific preventive and treatment strategies for this devastating disease.
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA.|The Bloomberg Children's Center, 1800 Orleans Street, Baltimore, Maryland 21287, USA.
authors.forename: Diego F
authors.initials: DF
authors.lastname: Niño
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA.|The Bloomberg Children's Center, 1800 Orleans Street, Baltimore, Maryland 21287, USA.
authors.forename: Chhinder P
authors.initials: CP
authors.lastname: Sodhi
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA.|The Bloomberg Children's Center, 1800 Orleans Street, Baltimore, Maryland 21287, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hackam
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001942:Breast Feeding; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D020345:Enterocolitis, Necrotizing / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D000069196:Gastrointestinal Microbiome / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D019936:Probiotics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001685:Biological Factors; D015415:Biomarkers