Experimental colitis delays and reduces the severity of collagen-induced arthritis in mice

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.

A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?

“…Gevers et al [59] reported G. moribillum to be present in higher abundance in CD compared to controls. Interestingly, a recent experimental colitis study has reported that Gemella , in addition to Ruminococcus and Blautia, were overrepresented in the arthritis and colitis group versus arthritis only, at 41 days post-induction [61]. There are numerous environmental and genetic risk factors that are known to influence IMID.…”

Rifaximin Alters Intestinal Microbiota and Prevents Progression of Ankylosing Spondylitis in Mice

“…The decalcified tissues were embedded in paraffin, and sectioned 5 μm and stained with hematoxylin and eosin. The histological arthritis score was determined in a blinded manner for changes in synovial inflammation, cartilage degradation, and bone erosion as previously described(Ishikawa et al, 2016; Hablot et al, 2017). Synovial inflammation was scored as following scale: 0 = normal, 1 = slight thickening of the lining layer with some infiltrating cells in the sublining layer, 2 = moderate thickening of the lining layer with a moderate number of infiltrating cells in the sublining layer, 3 = severe inflammation with a massive immune cell infiltrate into the synovium.…”

The Dynamic Interplay between the Gut Microbiota and Autoimmune Diseases

“…For instance, the abundance of Prevotella copri is increased in some patients with early-stage RA, but Prevotella histicola from the human gut microbiota suppresses the development of RA [58]. Interestingly, Hablot et al evaluated the impact of experimental colitis on the development of CIA in mice and observed that concomitant experimental colitis reduced severity in association with modification of the gut microbiota composition [59].…”