Neuro-Immune Interactions in the Gut

Summary

Hirschsprung's disease (HD) is diagnosed shortly after birth and is characterized by the presence of megacolon. HD is caused when ganglion cells of the enteric nervous system (ENS) in the wall of the large intestine do not develop before birth. This results in a lack of gastrointestinal motility and leads to stool obstruction. It is known that ablation of enteric nerves is associated with intestinal infection and inflammation. Indeed the most severe complication in HD is Hirschsprung's associated enterocolitis (HAEC), characterized by explosive diarrhea, abdominal distension, fever and impending septic shock. Bacteria overgrowth and changes in colonic mucosal immune cell populations during HAEC suggest a possible defect in mucosal immune homeostasis. Under steady state conditions, the mucosal immune system must be tightly controlled to avoid harmful reactions against commensal flora and food antigens, while allowing protective immune responses against invading pathogens. This balance between tolerance and defense is influenced by the mucosal microenvironment, which in turn determines the phenotype and stability of mucosal immune cell populations. The goal of this project is to understand if the enteric nervous system plays a role in regulating mucosal immunity and how this might contribute to the development of HAEC.

Conditions

• Hirschsprung's Disease Associated Enterocolitis

Sponsors & Collaborators

• University Children's Hospital, Zurich

  collaborator OTHER

• Insel Gruppe AG, University Hospital Bern

  collaborator OTHER

• Kinderspital St. Gallen

  collaborator UNKNOWN

• Bâtiment Hospitalier CHUV

  collaborator UNKNOWN

• Universität Klinikum Heidelberg

  collaborator UNKNOWN

• Luzerner Kantonsspital

  collaborator OTHER

• Hôpitaux Universitaires Genève

  collaborator UNKNOWN

• Ospedale Regionale di Bellinzona e Valli

  collaborator UNKNOWN

• University Children's Hospital Basel

  lead OTHER

Principal Investigators

• Stefan Holland-Cunz, Prof · University Children's Hospital Basel

Eligibility

Min Age

0 Months

Max Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2015-02-28

Primary Completion

2022-02-28

Completion

2022-02-28

Countries

• Germany
• Switzerland

Study Locations