Host-microbiota Interactions in Auto-inflammatory Diseases

Overview

Autoinflammatory diseases (AID) are genetic diseases responsible for excessive activation of innate immunity leading to blood inflammation and systemic symptoms. Most patients display digestive involvements that may resemble inflammatory bowel disease. Several studies have found dysbiosis in some AID. Gut microbiota can communicate with the host via gut-derived metabolites (Fatty acids, tryptophan, bile acids) that may have either pro-inflammatory or anti-inflammatory effects. Some metabolites can also activate the Aryl hydrocarbon receptor (AhR) pathway, which enhances gut barrier. Gut barrier dysfunction has already been associated with AID. Therfore, dysbiosis could promote digestive and inflammatory involvements in genetically predisposed patients via perturbations of gut-derived metabolites.

Detailed description

Patients will receive oral and written information about the research during a routine consultation.

A 10mL urine tube will be collected for research. A stool collection kit including a self-questionnaire to be filled out on the day of the stool collection will be given to all included patients to be collected on site or at home within three months after inclusion and to be returned to the laboratory by mail using a pre-stamped envelope provided at the time of inclusion and a self-questionnaire to be filled out on the day of the stool collection Blood and urine samples will be brought by an accredited carrier to the laboratory "Microbiota, Intestine and Inflammation"; UMRS-938 Sorbonne University, Hôpital Saint-Antoine where they will be analyzed. Stool samples will be sent by mail for stool samples.

If blood sampling is planned as part of routine care, 3 additional tubes (15mL, one dry tube of 5mL, 2 EDTA tubes of 5mL each) of peripheral blood will be collected.

Primary outcome measures

• Stool and blood Gut-derived metabolites in patients with AID [Time frame: 3 months]
• Stool and blood Gut-derived metabolites in patients with AID [Time frame: 3 months]

Secondary outcome measures (5)

• Role of AhR on activation of inflammatory pathways [Time frame: during the inclusion visit, baseline, day 1]
• Microbiota in AID patients [Time frame: 3 months]
• Effect of gut-derived metabolites on inflammatory pathways though cytokine production [Time frame: 3 months]
• Association of microbiota profile with biological control of the disease [Time frame: 3 months]
• Association of microbiota profile and severity of the disease [Time frame: 3 months]

Eligibility criteria

Inclusion criteria

• Patients with autoinflammatory diseases aged >12 years and followed in the CEREMAIA internal medicine department present for consultation or day hospital for a routine care visit.
• FMF defined by the Eurofever/PRINTO criteria
• or CAPS définie by the Eurofever/PRINTO criteria
• or MKD defined by the Eurofever/PRINTO criteria
• or - DADA2 defined by the presence of two mutations in the ADA2 gene with pathogenicity of at least ≥ 3
• or - HA20 defined by the presence of one TNFAIP3 mutation with pathogenicity of at least ≥ 3
• or - JAAD defined by the presence of one JAK1 mutation with pathogenicity of at least ≥ 3
• or Juvenile polyarthritis defined by the presence of one LACC1 mutation with pathogenicity of at least ≥ 3
• or - Unclassified AMI defined by:

• Fever +/- systemic symptoms Recurrent
• Biological inflammation (CRP>20mg/l) in crisis or permanent
• Absence of pathogenic mutation highlighted by current next-generation sequencing techniques in known autoinflammatory disease genes
• Collection of non-opposition to participation in research and specific consent for the biological collection of the patient or their legal representative in the case of a minor patient
• Lack of legal protection
• Patients benefiting from a social security scheme

Exclusion criteria

• Antibiotic therapy within 3 months prior to inclusion. If antibiotic therapy was initiated between inclusion and stool collection (data collected on the self-administered questionnaire accompanying the stool collection), the analysis data performed prior to antibiotic therapy will be retained, and the stool will not be analyzed.
• Current infection on the day of inclusion
• No social security
• Refusal to participate

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

France · 1 center

• Internal medicine, Tenon Hospital (APHP) — Paris

Identifiers

NCT: NCT07718555 · APHP230035 · IDRCB 2025-A01478-41

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗