Background/Purpose: Rheumatoid arthritis (RA) is a systemic autoimmune disease that is thought to originate at the mucosa. Despite the mucosa’s importance, few studies have examined the microbiome of the intestinal mucosa in patients with RA, instead assessing stool microbiome as a surrogate. The purpose of this pilot study is to determine if the mucosal microbiome differs in patients with RA compared to control participants and by site.

Methods: Patients with RA and without RA or other inflammatory autoimmune disease who were undergoing routine colonoscopy were recruited at Vanderbilt University Medical Center as part of the Vanderbilt GI Repository. Mucosal tissue biopsies were obtained from terminal ileum, and ascending, transverse and descending colon. Specimens were flash frozen immediately after collection and stored at -80°C until processing. DNA was extracted from all four mucosal biopsy samples and 16S rRNA long-read DNA sequencing (V1-V8 regions) was performed using Oxford Nanopore Technology. Counts of bacterial taxa were compared using DESeq2 and the Benjamini-Hochberg method was used to adjust for multiple comparisons with a false discovery rate at 5%.

Results: This pilot study included 5 RA (mean age 56 ± 14 years, 100% female) and 5 control (mean age 44 ± 21 years, 60% female) participants. Measures of alpha diversity across sites were not significantly different in RA vs control participants; however, there were significant differences in the microbiome composition at the 4 mucosal sites. At all sites, Prevotella, Christensenellales, Megaspharera massiliensis, and Odoribacter splanchnicus were significantly decreased in RA versus control participants. Within all sites of the colon Eubacterium callanderi, Veillonella and Bacteroides ovatus were increased, and Shigella dysenteriae was decreased significantly in RA versus control participants. While there were these commonalities by site, there were many site-specific significant alterations in mucosal microbiome (Figure).

Conclusion: Several taxa including Prevotella and Christensenellales were decreased at all mucosal sites in patients with RA versus control participants, while there were many site-specific mucosal microbiome alterations. Further studies will be needed to validate these findings in a larger cohort and to assess whether mucosal site-specific alterations in microbiome are associated with development of RA, disease activity and features.

Figure: Mucosal site-specific microbiome alterations in patients with RA versus control participants

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pilot-study-demonstrates-altered-intestinal-mucosal-microbiome-in-patients-with-rheumatoid-arthritis-versus-control-subjects/