Host-microbiota-environment Interactions (MIP-1)

Study of the Determinants of Pediatric Onset Inflammatory Diseases: Host-microbiota-environment Interactions

Two types of inflammatory and autoimmune diseases (excluding monogenic diseases) can be distinguished in children: those similar to adult diseases but with an early onset (type 1 diabetes, inflammatory diseases of the gastrointestinal tract, rheumatoid arthritis with anti-CCP antibodies) and those specific to children that are not described in adults (early-onset juvenile idiopathic arthritis with anti-nuclear and anterior uveitis).

The familial and nosological aggregations suggest that these diseases are probably polygenically determined, and result from interactions with the environment. In a singular way, the incidence of "adult" diseases is increasing while the age of onset is getting earlier; conversely, there is no increase in early-onset juvenile idiopathic arthritis.

On the other hand, the influence of early events that may alter the microbiotic environment is different for different diseases: whereas cesarean section (or early antibiotic therapy) has been shown to increase the risk of JIA and T1DM, it does not seem to change the risk of IBD. We hypothesize that environmental factors, particularly those related to diet and bacterial and fungal digestive microbiota - are different between these disease categories.

Study Overview

• Status: Terminated
• Conditions: Inflammatory Bowel Diseases; Diabetes type1; Juvenile Idiopathic Arthritis
• Intervention / Treatment: Other: Stool sample

Detailed Description

Exploratory pathophysiology monocentric study including an initial case-control study, followed by a cohort for cases.

Controls will be siblings of cases with longitudinal follow-up.

Stool samples will be collected simultaneously from the child with JIA, T1DM or IBD (case) and his/her sibling(s) (control):

• at the time of diagnosis
• two months after diagnosis (for children with inflammatory disease only)
• one year after diagnosis (cases and controls)

Tryptase level in plasma will be recorded for the child with JIA, T1DM or IBD (at the time of diagnosis, 2 months and 1 year after diagnosis)

• Study Type: Observational
• Enrollment (Actual): 4

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63000
    • CHU de Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 6 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The participants include patient-sibling pairs meeting the inclusion criteria (30 children newly diagnosed with JIA, IBD or T1DM and 30 siblings).

Description

Inclusion Criteria:

CASE:

- Newly diagnosed with JIA, IBD or T1DM

CONTROL:

- Brother/sister of child with pediatric onset inflammatory disease (same age category - same environment: diet, living environment)

Exclusion Criteria (case and control):

• Child with antibiotic treatment in the 4 weeks preceding the stool sample
• Recent digestive infectious disease (bacterial, viral, parasitic) (end of episode < 7 days)

Exclusion Criteria (control): children with autoimmune or inflammatory disease

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental; Child under 10 years old newly diagnosed with JIA, IBD or T1DM	Other: Stool sample; Comparaison of the gut microbiota composition
Active Comparator: Healthy control; Brother/sister of child with pediatric onset inflammatory disease (same age category - same environment: food, living space)	Other: Stool sample; Comparaison of the gut microbiota composition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiota composition	Variation between cases and controls in gut microbiota composition (determination of the gut microbiota composition by 16S metagenomic)	Day 1
Gut microbiota composition	Variation between cases and controls in gut microbiota composition (determination of the gut microbiota composition by 16S metagenomic)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composition of the fecal volatolome	The volatile compounds in the samples will be analyzed via solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (GC-MS)	Day 1
Variation in gut microbiota following initiation of therapy in patients newly diagnosed with JIA, IBD or T1DM.	Characterization of the gut microbiota using a capture method by hybridization of the gene encoding 16S rRNA	Day 1, 2 months, 12 months
Tryptasemia	Variation in plasma tryptase levels during the first year of the disease	Day 1, 2 months, 12 months
Fecal contamination with nanoparticles	measurement of titane and silicia levels in stool sample	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
• Investigators: Principal Investigator: Etienne Merlin, University Hospital, Clermont-Ferrand

Publications and helpful links

General Publications

• Schwiertz A, Jacobi M, Frick JS, Richter M, Rusch K, Kohler H. Microbiota in pediatric inflammatory bowel disease. J Pediatr. 2010 Aug;157(2):240-244.e1. doi: 10.1016/j.jpeds.2010.02.046. Epub 2010 Apr 18.
• Di Paola M, Cavalieri D, Albanese D, Sordo M, Pindo M, Donati C, Pagnini I, Giani T, Simonini G, Paladini A, Lionetti P, De Filippo C, Cimaz R. Alteration of Fecal Microbiota Profiles in Juvenile Idiopathic Arthritis. Associations with HLA-B27 Allele and Disease Status. Front Microbiol. 2016 Oct 26;7:1703. doi: 10.3389/fmicb.2016.01703. eCollection 2016.
• Defois C, Ratel J, Garrait G, Denis S, Le Goff O, Talvas J, Mosoni P, Engel E, Peyret P. Food Chemicals Disrupt Human Gut Microbiota Activity And Impact Intestinal Homeostasis As Revealed By In Vitro Systems. Sci Rep. 2018 Jul 20;8(1):11006. doi: 10.1038/s41598-018-29376-9.
• Rouxel O, Da Silva J, Beaudoin L, Nel I, Tard C, Cagninacci L, Kiaf B, Oshima M, Diedisheim M, Salou M, Corbett A, Rossjohn J, McCluskey J, Scharfmann R, Battaglia M, Polak M, Lantz O, Beltrand J, Lehuen A. Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. Nat Immunol. 2017 Dec;18(12):1321-1331. doi: 10.1038/ni.3854. Epub 2017 Oct 9.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2022
• Primary Completion (Actual): July 12, 2022
• Study Completion (Actual): July 12, 2022

Study Registration Dates

• First Submitted: December 14, 2021
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: environmental factors; microbiota; food contaminants
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Intestinal Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Skin and Connective Tissue Diseases; Arthritis, Juvenile; Inflammatory Bowel Diseases
• Other Study ID Numbers: RNI 2021 MERLIN; 2021-AO1006-35 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No