Background: Inflammatory bowel disease (IBD)-associated arthritis, an extra-intestinal manifestation (EIM), affects over 25% of those with IBD. The gut microbiome, which varies at different locations within the intestinal tract, is thought to play a key role in IBD development, but the precise mechanisms remain obscure.
Aim: To characterize the relationship between IBD-associated arthritis and the intestinal microbiome.
Methods: Microbiome analyses were performed on 16S rRNA V3V4 amplicon sequence data generated from endoscopic mucosal biopsies taken from the terminal ileum (TI), hepatic flexure (HF), and distal descending colon (DDC) of participants enrolled in the LOCATION-IBD cohort. Alpha diversity was assessed using Shannon index and beta diversity was assessed using Jenson-Shannon Divergence (JSD). ALDEx2 was used to assess differential bacterial taxa amplicon sequence variants (ASVs) relative abundances between those with vs without IBD-associated arthritis. Generalized linear models (GLM, binomial) were used to assess the relationship between central log-transformed abundance data and joint manifestations, while controlling for IBD type, biopsy location, and whether biopsies were from a site of inflammation.
Results: For analysis, we included mucosal biopsies from subjects in the LOCATION-IBD cohort with (n= 140 from 51 subjects) and without (n = 300 from 104 subjects) joint EIMs and with joint pain of unclear etiology (n= 53 from 518 subjects). Results clustered based on participant, and similar genera and ASVs were present across TI, HF, and DDC mucosal samples. Shannon diversity was similar across samples, regardless of arthritis category, though diversity was lower in those with Crohn’s disease than ulcerative colitis. At the bacterial genera level, JSDs between samples for an individual participant were higher for those with IBD-associated arthritis. Based on ALDEx2 comparisons, abundances of multiple Corynebacterium ASVs were increased in those with joint EIMs, whereas Roseburia ASVs were reduced. GLMs of joint manifestations, accounting for IBD type, sampling location, and active inflammation, revealed an association between Corynebacterium ASVs and joint manifestations, while Roseburia ASVs were associated with samples from those without IBD-associated arthritis.
Conclusions: This is the first study to compare the intestinal mucosal microbiome across several locations in subjects with and without IBD-associated arthritis. Similar bacteria were found across the terminal ileum, proximal colon, and distal colon in individuals, but lower concordance was seen in those with IBD-associated arthritis. Notably, the relative abundance of Corynebacterium and Roseburia ASVs was altered in those with vs without joint manifestations; these bacteria represent promising targets for future studies.

Raymond K. Cross

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