Background/Purpose: Alterations in resident bacteria, termed dysbiosis, is present in patients in early stages of rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis. However, it remains unclear if dysbiosis is causative or occurs as a result of the disease. Using the collagen-induced arthritis (CIA) model in mice, we aimed to determine if microbiome changes occur and, if so, at what point during the development of disease.

Methods:  DBA1/j mice were injected intradermally with bovine type II collagen emulsified in complete Freund’s adjuvant at days 0 and 21 to induce CIA. Fecal pellets were harvested from the mice at days 0, 21, and 39 after immunization. The microbial DNA was extracted from the feces using a commercially available kit. 16S rRNA sequencing was performed and the sequences aligned using SINA with a reference taxonomic database Silva 111 NR. Microbial ecology such as diversity and relative abundance of the 16S rRNA sequences was evaluated using Explicet software. Statistical analyses of the changes in identified species were done by non-parametric ANOVA.

Results:  The mean arthritis severity in our cohort of mice at day 39 after immunization was 6.67 ± 1.05 (based on a scale of 0-12); no mice had observable arthritis before day 24. Our microbiome sequencing results demonstrate significant differences in the beta diversity of the microbial community at day 0 (1.000) compared to day 21 (0.866) and at day 39 (0.920). We now plan to evaluate the relative abundance of specific bacterial species at each of our time points.

Conclusion: These data indicate that dysbiosis occurs during the initial stages of CIA, when immune responses that lead to disease are developing. Such findings suggest that dysbiosis may be causative in pathogenesis of disease rather than reflective of the disease presence. An interesting finding was that beta diversity was most affected at day 21 compared to day 39. This is consistent with microbiome studies in patients with RA in which dysbiosis were most pronounced in new-onset patients compared to those with established disease. With our additional analyses, we expect to identify changes in specific bacterial species that may shed light on the role of the microbiome in developing arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/alterations-in-the-colonic-microbiome-precede-the-development-of-murine-inflammatory-arthritis/