Background/Purpose: Rheumatoid arthritis (RA) is an autoimmune disease with an unknown cause. Observations of dysbiosis and mucosal inflammation in patients with RA has raised interest in studying microbial-mucosal interactions as a potential trigger of RA. Using the murine collagen-induced arthritis (CIA) model, we hypothesized that microbiota and mucosal inflammation are required for the development of autoimmune arthritis.

Methods:  4-6 DBA1j mice were treated with or without broad-spectrum antibiotics in the drinking water 7 days preceding and throughout the induction of CIA, by immunization of bovine type II collagen (CII) in Complete Freund’s Adjuvant (CFA) on days 0 and 21. Fecal pellets and sera were collected every 7 days during the study for microbiome analysis and autoantibody development. Mice were euthanized on days 21 or 35 for tissue analyses for cytokines and autoantibodies by ELISA. Microbiome analyses were performed on fecal pellets by 16S sequencing of the bacterial rRNA.

Results:  During the preclinical phase of CIA (without antibiotics), we find remarkable changes in the intestinal microbiome, specifically increased Clostridia and decreased Lactobacillus and Bacteroides. In parallel, intestinal permeability and cytokines IL-12 and IL-1β increased significantly (P value < 0.05). Furthermore, anti-CII autoantibodies were increased within the intestine, suggesting a developing mucosal immune response. In microbiota-depleted mice (antibiotic treated), CIA severity was reduced by 50% as assessed by clinical scores (P value < 0.01). Correspondingly, tissue cytokines and both serum and fecal anti-type II collagen antibody levels were reduced.

Conclusion: Taken together, these data suggest a model in which intestinal dysbiosis and mucosal immune responses drive the development of autoimmune arthritis. Future studies are aimed at elucidating the pathway by which microbiota and mucosal immune responses stimulate systemic autoantibody production that is necessary for the development of CIA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/role-of-microbiota-in-development-of-autoimmune-arthritis/