Pathogenesis of neonatal necrotizing enterocolitis

Abstract

Although necrotizing enterocolitis (NEC) is the most lethal gastrointestinal disease in the neonatal population, its pathogenesis is poorly understood. Risk factors include prematurity, bacterial colonization, and formula feeding. This review examines how mucosal injury permits opportunistic pathogens to breach the gut barrier and incite an inflammatory response that leads to sustained overproduction of mediators such as nitric oxide and its potent adduct, peroxynitrite. These mediators not only exacerbate the initial mucosal injury, but they also suppress the intestinal repair mechanisms, which further compromises the gut barrier and culminates in bacterial translocation, sepsis, and full-blown NEC.

Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling

“…Indeed, in the formula-feeding-hypoxia neonatal rat model of NEC, DCA levels are elevated (vs. dam-fed littermates) in the lumen of the terminal ileum by 24 -48 h (26, 27), while histological damage is not seen until 72 h. DCA levels are much lower in human infants that are breast-fed (29), and breast feeding has long been considered protective from NEC (45).…”

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

“…Maternal pathogen-induced inflammation potentially contributes to both preterm birth and fetal inflammatory responses (2). This detrimental inflammation results in significant deterioration of the microbial consortium of the neonatal gut (3) that skews immunity toward proinflammatory responses, possibly resulting in necrotizing enterocolitis (NEC), a potentially fatal inflammatory bowel necrosis primarily affecting preterm infants with risk factors (e.g., intestinal injury) (4). While the multifactorial mechanisms involved in NEC and potential therapeutic approaches remain elusive (5), the need for novel therapeutic interventions that redirect inflammation and reduce disease severity, leading to its regression, is urgent (6).…”

A Practical Approach to Emergencies in the Neonatal Period

“…Infants with NEC can appear ill, with lethargy, irritability, anorexia, a distended abdomen, and bloody stools. Mortality is high (between 20% and 40%) [32].…”

“…A complete blood cell count can show leukocytosis and anemia, as well as thrombocytopenia, which are a hallmark of NEC; a blood culture should be obtained prior to starting antibiotics. Serum electrolytes can show hyponatremia, which is poor prognostic indicator of capillary fluid leakage in the bowel, as well as signs of acidosis [32].…”