Host-microbiota-environment Interactions

Study Overview
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Brief Summary
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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.

Detailed Description
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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)

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

Conditions
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Juvenile Idiopathic Arthritis, Diabetes type1, Inflammatory Bowel Diseases

Intervention / Treatment
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* Other: Stool sample


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiota, environmental factors, food contaminants