Hirschsprung's associated enterocolitis

Abstract

Purpose of Review Hirschsprung’s Disease (HSCR) is characterized by an absence of ganglion cells in the distal hindgut, extending from the rectum to a variable distance proximally, and results from a failure of cranial-caudal neural crest cell migration. Hirschsprung’s-Associated Enterocolitis (HAEC) is a condition with classic manifestations that include abdominal distention, fever and foul-smelling stools, and is a significant and life-threatening complication of HSCR. The purpose of this review is to critically evaluate recent findings regarding the pathophysiology of HAEC. Recent Findings Several recent studies have investigated the etiology of HAEC in humans and mouse models. These studies suggest that alterations in the intestinal barrier, including goblet cell number and function and Paneth cell function, impaired gastrointestinal mucosal immunity, including B-lymphocyte trafficking or function and secretory IgA production, and dysbiosis of the intestinal microbiota may contribute to the development of HAEC. Summary Recent studies add to the body of literature suggesting that the intestinal defects observed in HSCR are not restricted to the aganglionic segment but extend to the mucosal immune system within and beyond the gastrointestinal tract. Future studies further dissecting mechanisms of HAEC and validating these findings in human patients will allow for development of directed therapeutic interventions.

Swimming motility of a gut bacterial symbiont promotes resistance to intestinal expulsion and enhances inflammation

“…To test this expulsion-based mechanism more directly, we assessed whether the abundance of Δmot and Δche could be rescued in ret −/− mutant zebrafish hosts, which have reduced intestinal transport because of a dysfunctional enteric nervous system [32,42]. Humans with ret mutations can develop Hirschsprung disease, which is an affliction characterized by intestinal dysmotility and altered gut microbiome composition [43,44]. Strikingly, we found that the intestinal abundances of both Δmot and Δche were fully rescued to wild-type levels in ret −/− mutant animals ( Fig 3B).…”

The first Korean case of Waardenburg-Shah syndrome with novel endothelin receptor type B mutations

“…It may be possible that the spleen torsion of our patient is related to altered endothelin receptor type B function due to EDNRB mutations. Also, in patients with Hirschsprung's disease, altered goblet cell structures and functions in aganglionic segments of bowel may be responsible for the recurrent enterocolitis [16]. The complex interactions between EDNRB mutations, immune dysfunction, and changes in gut functional conditions due to Hirschsprung's disease could be associated with recurrent enteritis shown in our patient.…”

Is intestinal stasis sufficient by itself in promoting enterocolitis in a non-genetic rat model of Hirschsprung’s disease?

“…These can be caused by variations in the components and amount of mucus, immunological deficiency, either local or systemic, with deficient white cell function, mucosal immunity defects, increased prostaglandin E1 activity, impaired motility associated with protein sensitization, and sucrase-isomaltase deficiency. 11,12,[16][17][18][19][20] These conditions could be the expression of the complex genetics of HD. 21 Increased HE risk in patients with Down syndrome, 22,23 cartilage-hair hypoplasia, 24 family history of HD, and female sex point to a possible genetic contribution to the etiology of HE.…”