Fig. 2: The neonatal intestinal epithelium during necrotizing enterocolitis.

Injury to the developing intestinal epithelium underlies the pathophysiology of necrotizing enterocolitis (NEC, circular inset). Preterm neonates are at risk for NEC due to a myriad of factors related to their stage of intestinal development and critical illness. When an infant is delivered preterm, their intestinal epithelium is composed of lower numbers of mature specialized epithelial cells relative to term infants. For example, lower goblet and Paneth cell numbers are associated with associated impairments in mucus and antimicrobial peptide production. These deficits lead to an increase in potentially pathogenic Gram-negative bacteria in the intestinal lumen. These bacteria can activate TLR4 signaling on the intestinal epithelium leading to the induction of an inflammatory cascade. Inflammation subsequently results in patchy intestinal epithelial injury, reduced barrier integrity, and translocation of bacteria from the intestinal lumen. When this occurs, infants are also at risk for sepsis, irreparable intestinal injury, and death. Figure created with Biorender.com.