Abstract
Amongst extraintestinal manifestations (EIM) occurring in IBD patients, rheumatologic manifestations are the most frequent. Understanding the relationships between arthritis and colitis is a prerequisite to improving the management of these patients. Microbiota of patients with IBD or rheumatologic diseases, like spondyloarthritis (SpA) is modified compared to healthy individual. Thus, we have evaluated the impact of colitis in the development of arthritis in mice and we have analyzed microbiota changes. Collagen-induced arthritis (CIA) was induced at day 0 in DBA1 mice exposed or not to Dextran Sodium Sulfate (DSS) to induce colitis between day 14 and day 21. Animals were monitored regularly for arthritis and colitis severity (clinical score, hindpaw edema). Fecal microbiota was studied by 16S rRNA deep sequencing at critical time points (D14, D14, D21 & D41). At day 41, histological scoring of the intestines and ankles were performed at the end of experiment. Induction of colitis slightly delayed arthritis onset (2 ± 1 days of delay) and reduced its severity (5.75 ± 1.62 in arthritis only group vs 4.00 ± 1.48 in arthritis + colitis group (p = 0.02 at day 28) macroscopically and histologically. In contrast, colitis severity was not influenced by arthritis development. Induction of colitis promoted a modification of microbiota composition and a decrease of α-diversity. Fecal microbiota composition was different between “colitis” and “arthritis+colitis” groups during colitis development. Interestingly a milder decrease of bacterial diversity in the “arthritis+colitis” group was observed. Concomitant experimental colitis protects mice against collagen-induced arthritis and this is associated with changes in gut microbiome composition.
Highlights
Inflammatory bowel diseases (IBD) affecting over 1 million individuals in the USA and 2.5 million in Europe [1]
We evaluated for the first time, the impact of experimental colitis in the development of collagen-induced arthritis in mice and the associated gut microbiota changes
Understanding the mechanisms underlying the development of such complication in IBD is a prerequisite to improving their management and remains an unmet need for these patients
Summary
Inflammatory bowel diseases (IBD) affecting over 1 million individuals in the USA and 2.5 million in Europe [1]. The two main IBD are Crohn’s disease (CD) and ulcerative colitis (UC). Patients with IBD, known to be systemic disorders, are likely to develop extraintestinal manifestations (EIMs). EIMs have a prevalence rate ranging from 6% to 47%. One third of IBD patients will develop EIMs in the course of their disease [2,3,4]. Joint involvement (Spondyloarthritis SpA) is the most common EIM in patients with IBD, with a prevalence ranging between 17% and 39% [8]. This comorbidity can be very disabling and is associated with a more severe disease course in IBD patients [5]
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