Host-microbiota Interactions in Auto-inflammatory Diseases (HO-MICRO-MAI)

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.

Study Overview

• Status: Recruiting
• Conditions: Autoinflammatory Diseases

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.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Sophie GEOGIN-LAVIALLE, MD PhD; Phone Number: +33 01 56 01 70 82; Email: sophie.georgin-lavialle@aphp.fr
• Study Contact Backup: Name: Inès ELHANI, MD; Phone Number: +33 01 56 01 70 82; Email: ines.elhani@aphp.fr

Study Locations

• France
  • Paris, France, 75020
    • Recruiting
    • Internal medicine, Tenon Hospital (APHP)
    • Contact: Inès ELHANI, MD; Phone Number: +33 01 56 01 70 82; Email: ines.elhani@aphp.fr
    • Contact: Sophie GEORGIN-LAVIALLE, MD, PhD; Phone Number: +33 01 56 01 70 82; Email: sophie.georgin-lavialle@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with auto-inflammatory diseases (Familial Mediterranean Fever, Mevalonate kinase deficiency, Cryopyrin-associated periodic fever, A20 haploinsufficiency, ADA2 deficiency, LACC1-associated juvenile arthritis, JAK1-associated autoinflammatory disease, or Syndrome of Undifferentiated Recurrent Fever ) followed up in the French reference center of autoinflammatory diseases.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with autoinflammatory diseases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool and blood Gut-derived metabolites in patients with AID	Quantification of gut-derived metabolites in stools using mass spectrometry	3 months
Stool and blood Gut-derived metabolites in patients with AID	Qualitative evaluation of gut-derived metabolites in stools	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Role of AhR on activation of inflammatory pathways	Quantification of pro-inflammatory cytokines in presence of AhR agonists on patients' monocytes	during the inclusion visit, baseline, day 1
Microbiota in AID patients	Dysbiosis measured by alpha and betadiversity	3 months
Effect of gut-derived metabolites on inflammatory pathways though cytokine production	Increase or decrease in proinflammatory cytokines secreted	3 months
Association of microbiota profile with biological control of the disease	Correlation between microbiota profiles and inflammation biomarkers (C-reactive protein, Serum A Amyloid, proteinuria)	3 months
Association of microbiota profile and severity of the disease	Correlation between microbiota profiles and complications (AA Amyloidosis, Cirrhosis)	3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Sophie GEORGIN-LAVIALLE, APHP

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: April 20, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Microbiota; Gut; Autoinflammatory diseases
• Other Study ID Numbers: APHP230035; IDRCB 2025-A01478-41 (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