MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung's Associated EnteroColitis (MICROPRUNG)

Hirschsprung disease is a congenital abnormality due to the lack of migration of neural crest cells in myenteric and submucosal plexi of the bowel wall. The consequence is the absence of parasympathetic control of the distal bowel from the anal sphincter to various levels. The most common type of Hirschsprung disease alters the rectosigmoid (80%). The incidence is around 1/5000 live births. This anomaly requires a surgical ablation of the aganglionic segment.

Regardless of the surgical complications, patients with Hirschsprung disease are exposed to the risk of Hirschsprung Associated EnteroColitis (HAEC). This variable risk, 4-54%, is responsible to a major part of Hirschsprung disease morbimortality. Its onset is more frequent during the first two years of life and then decrease with age.

Its pathogenesis remains unclear but could be due to intestinal homeostasis breakdown that involves microbiota, intestinal barrier, immune system and enteric nervous system. This breakdown of the mutual benefit relation due to microbiota or bowel anomaly is known to be responsible of Crohn's disease onset. Some studies emphasize the role of microbiota in the pathogenesis of HAEC, but the techniques or the methodology with small numbers of patients limit any conclusion or clinical use.

The study hypothesizes microbiota is a major factor in HAEC onset and in their functional bowel problems. Considering HAEC is more frequent the first two years, it's thought that intestinal microbiota changes with time in those patients. This project is innovative because it will use high throughput sequencing methods and analysis for microbiome analysis on fecal samples from a multicenter cohort of patients at various ages.

Multicentre transversal study.

This study has the potential to significantly modify clinical practice for Hirschsprung disease patients: a better care for HAEC and functional troubles thanks to a better understanding of their microbiota, targetted antibiotic treatment for HAEC, prophylactic treatment of patients at high risk of HAEC.

Study Overview

• Status: Completed
• Conditions: Hirschsprung Disease
• Intervention / Treatment: Other: Fecal samples

Detailed Description

Primary objective :

Characterize intestinal microbiota in patients with or without HAEC.

Secondary objectives :

• Look for a difference in microbiota composition between patients with or without HAEC ;
• Study the evolution with age of the microbiota in Hirschsprung disease patients ;
• Study predominant taxonomic classification elements in both groups.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49000
    • Angers University Hospital
  • Brest, France, 29000
    • Brest University Hospital
  • Caen, France, 14000
    • Caen Univeristy Hospital
  • Nantes, France, 44000
    • Nantes University Hospital
  • Poitiers, France, 86000
    • Poitiers University Hospital
  • Rennes, France, 35000
    • Rennes University Hospital
  • Tours, France, 37000
    • Tours University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients from 0 to 16 years ;
• With rectosigmoid Hirschsprung's disease confirmed by rectal biopsies and at surgery;
• Already operated on, whatever the surgical technique was ;
• With a health care insurance;
• Clear information and signed consent form

Exclusion Criteria:

• Long segment Hirschsprung disease ;
• Syndromic Hirschsprung disease ;
• Down syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Fecal samples; High throughput sequencing methods and analysis for microbiome analysis on fecal samples from a multicenter cohort of patients at various ages.	Other: Fecal samples; High throughput sequencing methods and analysis for microbiome analysis on fecal samples from a multicenter cohort of patients at various ages.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal microbiota composition	Characterize intestinal microbiota in patients with or without HAEC	Sampling day

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Alexis ARNAUD, MD, Rennes University Hospital

Publications and helpful links

General Publications

• Arnaud AP, Cousin I, Schmitt F, Petit T, Parmentier B, Levard G, Podevin G, Guinot A, DeNapoli S, Hervieux E, Flaum V, De Vries P, Randuineau G, David-Le Gall S, Buffet-Bataillon S, Boudry G. Different Fecal Microbiota in Hirschsprung's Patients With and Without Associated Enterocolitis. Front Microbiol. 2022 Jun 30;13:904758. doi: 10.3389/fmicb.2022.904758. eCollection 2022.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: August 2, 2016
• First Posted (Estimate): August 5, 2016

Study Record Updates

• Last Update Posted (Actual): September 13, 2018
• Last Update Submitted That Met QC Criteria: September 11, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Hirschsprung Associated EnteroColitis (HAEC)
• Additional Relevant MeSH Terms: Digestive System Diseases; Congenital Abnormalities; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Digestive System Abnormalities; Megacolon; Enterocolitis; Hirschsprung Disease
• Other Study ID Numbers: 35RC15_9873_MICROPRUNG; 2015-A01317-42 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Case Report Form