THE COLONIC MUCOSAL MICROBIOME IN IBD-ASSOCIATED ARTHRITIS IS MORE VARIABLE THAN IN IBD ALONE

Abstract

Abstract BACKGROUND Inflammatory bowel disease (IBD)-associated arthritis affects over 25% of those with IBD and is associated with several risk factors including disease location. The intestinal microbiome varies throughout the intestinal tract and is thought to play a role in the development of IBD, although the precise mechanism remains unexplored. To better characterize its relationship with IBD-associated arthritis, we analyzed the intestinal microbiome from a subset of subjects in the LOCATION-IBD cohort. METHODS Microbiome analysis was performed on 16S rRNA V3V4 amplicon sequencing data generated from mucosal biopsies from the terminal ileum (TI), hepatic flexure (HF), and the distal descending colon (DDC) of participants in the LOCATION-IBD cohort. Alpha diversity was assessed using the Shannon index, while beta diversity between samples from the same participant were assessed using Jenson-Shannon Divergence (JSD). ZicoSeq was used to assess differential abundances in composition between those with vs without IBD-associated arthritis. RESULTS In this analysis, we included a subset of samples from participants in the LOCATION-IBD cohort with (n= 68 from 25 participants) and without (n = 86 from 29 participants) joint EIMs and with joint pain of unclear etiology (n= 14 from 5 participants). Overall, samples clustered predominantly based on participant, and similar genera were present across TI, HF, and DDC mucosal samples. Shannon diversity was similar across samples, regardless of the associated arthritis category, though diversity was lower in those with CD compared to those with UC (p-value = 0.0007, Tukey post-hoc p-value = 0.0004) and trended to be higher in sites of inflammation (p-value = 0.0645). JSDs between samples for an individual participant were higher for those with compared to those without IBD-associated arthritis (p-value = 0.038). In those with joint EIMs, Flavonifractor and Fusicatenibacter were significantly lower without accounting for sampling location, whereas other species including Lachnoclostridium (increased) and Fusobacterium (decreased) were noted in the proximal colon. CONCLUSIONS To our knowledge, this represents the first assessment of the mucosal microbiome across several intestinal sites in individuals with and without IBD-associated arthritis. Our finding that similar bacteria are found across the terminal ileum, proximal colon, and distal colon, but that less site-to-site concordance is seen in those with IBD-associated arthritis, aligns with previous findings that the involvement of specific colonic segments is associated with IBD-associated arthritis. Further, our finding that the abundances of specific bacteria are altered, frequently in a site-specific manner, identifies potential opportunities for future studies.