Clinical trial NCT05176795: Host-microbiota-environment Interactions
Official title: Study of the Determinants of Pediatric Onset Inflammatory Diseases: Host-microbiota-environment Interactions
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Juvenile Idiopathic Arthritis
Diabetes type1
Inflammatory Bowel Diseases
Keywords: microbiota
environmental factors
food contaminants
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
First posted: 2022-01-04
Enrollment: 60
Sex: ALL
Minimum age (years): 0
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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).

Brief summary: 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: 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)

Eligibility criteria: 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

Primary outcomes:
measure: Gut microbiota composition
timeFrame: Day 1
measure: Gut microbiota composition
timeFrame: 12 months
Secondary outcomes:
measure: Composition of the fecal volatolome
timeFrame: Day 1
measure: Variation in gut microbiota following initiation of therapy in patients newly diagnosed with JIA, IBD or T1DM.
timeFrame: Day 1, 2 months, 12 months
measure: Tryptasemia
timeFrame: Day 1, 2 months, 12 months
measure: Fecal contamination with nanoparticles
timeFrame: Day 1
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Etienne Merlin
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.