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.

Necrotizing enterocolitis: Pathophysiology from a historical context

“…These findings provide insights into why the premature infant is at risk for NEC development, and why bacterial intestinal signaling is so much higher in the premature as compared with the full term population. These findings were explored in greater detail in a recent review from the Hackam group 49 .…”

Human Milk Oligosaccharides Increase Mucin Expression in Experimental Necrotizing Enterocolitis

“…Necrotizing enterocolitis (NEC) is a devastating inflammatory disease of the intestinal tract and a leading cause of death among preterm infants . Despite improvements in neonatal care, more than 30% of babies with NEC do not survive .…”

Brain Barrier Disruption and Region-Specific Neuronal Degeneration during Necrotizing Enterocolitis in Preterm Pigs

“…Necrotizing enterocolitis (NEC) is among the severest complications of preterm birth and is related to enteral feeding and bacterial colonization during the first days and weeks after birth [14]. Up to 7% of very preterm infants are affected by NEC, and mortality rates are as high as 30% [15].…”