The Role of Intestinal Microbiota Dysbiosis in the Development of Spondyloarthritis (RUMINOSPA)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Spondyloarthritis; Ruminococcus Gnavus
• Intervention / Treatment: Procedure: Biopsy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maxime BREBAN, MD, PhD; Phone Number: +33 1 49 09 56 72; Email: maxime.breban@aphp.fr

Study Locations

• France
  • Boulogne-Billancourt, France, 92100
    • Recruiting
    • Service de Rhumatologie, Hôpital Ambroise Paré, APHP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Maxime BREBAN, MD, PhD, Service de Rhumatologie, Hôpital Ambroise Paré, APHP

Publications and helpful links

General Publications

• Breban M, Tap J, Leboime A, Said-Nahal R, Langella P, Chiocchia G, Furet JP, Sokol H. Faecal microbiota study reveals specific dysbiosis in spondyloarthritis. Ann Rheum Dis. 2017 Sep;76(9):1614-1622. doi: 10.1136/annrheumdis-2016-211064. Epub 2017 Jun 12.
• Crost EH, Tailford LE, Monestier M, Swarbreck D, Henrissat B, Crossman LC, Juge N. The mucin-degradation strategy of Ruminococcus gnavus: The importance of intramolecular trans-sialidases. Gut Microbes. 2016 Jul 3;7(4):302-312. doi: 10.1080/19490976.2016.1186334. Epub 2016 May 25.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2021
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 16, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Microbiota; Spondyloarthritis; Dysbiosis; Ruminococcus gnavus
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Bone Diseases, Infectious; Spondylitis; Spondylarthritis; Dysbiosis
• Other Study ID Numbers: APHP210332; 2020-A03244-35 (Registry Identifier: IDRCB)

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