title: Established and emerging concepts in Hirschsprung's-associated enterocolitis.
abstract: Hirschsprung's disease (HSCR) is a common cause of neonatal bowel obstruction and the approach to diagnosis and surgical treatment is well defined and accepted. Hirschsprung's-associated enterocolitis (HAEC) remains a frequent cause of pre-operative and post-operative morbidity and mortality, with unchanged treatment guidelines over multiple decades. Recent advances in our understanding of the genetics underlying HSCR have allowed the development of animal models, some of which recapitulate the HAEC phenotype. These animal models, along with recent translational studies, have implicated multiple facets of mucosal immunity and microbiome dysbiosis in the development of HAEC. Here, we will review the established epidemiology, modes of diagnosis and treatment of HAEC. Furthermore, we will explore emerging concepts in the pathogenesis of this disease; including animal models, alterations in mucosal immunity, dysbiosis of the intestinal microbiome, specific genetic susceptibility, and novel treatment modalities.
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, University of Tennessee Health Sciences Center, Memphis, TN, USA. agosain@uthsc.edu.|Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, TN, USA. agosain@uthsc.edu.|Pediatric Surgery, University of Tennessee Le Bonheur Pediatric Specialists, 49 North Dunlap, Suite 266, Memphis, TN, 38105, USA. agosain@uthsc.edu.
authors.forename: Ankush
authors.initials: A
authors.lastname: Gosain
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006627:Hirschsprung Disease / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000628:therapy; D006801:Humans
keywords: Enterocolitis; Hirschsprung disease; Hirschsprung’s disease; Microbiome; Mucosal immunity; Pathogenesis