Hirschsprung disease (HSCR) is a common cause of neonatal bowel obstruction and is invariably lethal if untreated. HSCR results from failure of neural crest-derived cells (NCC) to migrate into and colonize the distal colon to form the enteric nervous system (ENS) which controls motility, secretion, digestion and absorption. NCC migration is governed by interactions between NCC and the extracellular matrix (ECM) in the surrounding intestinal microenvironment.

Hirschsprung-associated enterocolitis (HAEC) is a life-threatening complication of Hirschsprung Disease (HSCR). HAEC affects 30-60% of infants with HSCR and carries a mortality of 5-10%, with the majority of deaths occurring in newborns prior to definitive operation. Dysmotility, dysbiotic microbiota, impaired mucosal immunity, and intestinal barrier dysfunction all appear to contribute to the pathogenesis of HAEC.