The Role of Intestinal Microbiota Dysbiosis in the Development of Spondyloarthritis

Study Overview
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Brief Summary
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The primary objective of this case-control study aims to explore the role of bacterium Ruminococcus gnavus (R. gnavus) with intestinal biopsy and faecal sampling in the initiation and the development of spondyloarthritis (SPA) in comparison with health control subjets (patients without chronic disease but have indication to digestive endoscopy).

Detailed Description
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As secondary objectives, the study aims: to research the abundance of bacterial strain of R. gnavus in mucosal sampling by biopsy; to study the interaction between R. gnavus bacterium and mucus from histological sampling; to correlate the expression of genes of intestinal mucus with the variations of identified microbiota of mucus biopsy; to study the interaction between bacteria and intestinal epithelial cells during culture; to demonstrate perturbations of the immune responses by dysbiosis.

Official Title
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The Role of Dysbiosis of Intestinal Microbiota in the Development of Spondyloarthritis

Conditions
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Spondyloarthritis, Ruminococcus Gnavus

Intervention / Treatment
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* Procedure: Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with SPA: Patients ⩾ 18 years; Diagnosed as spondyloarthritis (SpA) according ASAS classification; Affiliated to a social security scheme; Have signed the written informed consent form. Control subjects: Subjects ⩾ 18 years; Subjects free of SPA and planned for a digestive endoscopy for another indication such as to explore the risk of colorectal cancer in family member; Affiliated to a social security scheme; Have signed the written informed consent form. Exclusion Criteria: Subjects unable to understand the proposed study and/or sign a informed consent form; Pregnant women or breast feeding women; Subjects under guardianship or curatorship; Have taken antibiotic 1 month prior to inclusion; Presenting acute or chronic severe pathology may likely to interfere with the interpret of outcome; Refusal of subjects to participate to the study; Foreign patients under french AME scheme.

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SPA patient<br>Patients with SPA | Procedure: Biopsy<br>* Biopsy during recto-coloscopy<br>|
| Sham Comparator: Subject without SPA<br>Health subjects without SPA, planned to undergo a digestive endoscopy. | Procedure: Biopsy<br>* Biopsy during recto-coloscopy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Isolation and characterization of R. gnavus | Isolation and characterization of R. gnavus bacterium from intestinal biopsy. | At the end of study, up to 2 years | 
| Bacteria analysis | Analysis of repartition of R. gnavus bacterium in each group and the comparison between 2 groups. | At the end of study, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bacterial strain's abundance | Compare the abundance by RT-q-PCR of bacterial strain (R. gnavus) between mucus biopsy sampling and faecal sampling, collected from PCR patients or control subjects respectively. | At the end of study, up to 2 years | 
| Mucin-degradation of Ruminococcus gnavus | Study the ability of the strain to grow on mucins of intestinal biopsy, colored after fixation to carnoy. | At the end of study, up to 2 years | 
| RNA sequencing analysis of biopsy | RNA sequencing analysis of rectal biopsy between SPA patients and control subjects. | At the end of study, up to 2 years | 
| Interaction between bacteria and intestinal epithelial cells | In order to study the interaction between bacteria and intestinal epithelial cells in culture (organoids). Study the induction of several target genes as peptides anti-microbians, mucin or chemokines by RT-q-PCR. | At the end of study, up to 2 years | 
| Dysbiosis-induced immune perturbations | To compare between 2 groups their reactivities of T cells from intestinal biopsy which contact with cells of exposed antigens in vitro, to R. gnavus stains or to other stains biopsied from control subjects. | At the end of study, up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spondyloarthritis, Ruminococcus gnavus, Microbiota, Dysbiosis