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P789 Microbiome composition is altered in patients with IBD independent of endoscopic activity

Boland K., Turpin W., Mohammadi A., Borowski K., Smith M.I., Nguyen G., Steinhart A.H., Croitoru K., Silverberg M.

Mount Sinai Hospital, Zane Cohen Center for Digestive Diseases, Toronto, Canada

Background

Genetic and microbial heterogeneity in inflammatory bowel disease (IBD) are likely important in pathogenesis and in determining phenotype classification into: Crohn's disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU). This study aims to characterise intestinal mucosal microbial profiles and potential association with IBD phenotypic characteristics.

Methods

IBD patients and healthy controls (HC) were recruited from a tertiary care IBD center on the day of colonoscopy performed for disease activity assessment. Clinical and demographic data were recorded. Quiescent IBD was defined as partial Mayo 0 or SES-CD 0–2. Amplicon sequencing of the V4 region of 16s rRNA bacterial DNA was completed on Illumina MiSeq platform and sequences processed using the QIIME pipeline. Alpha diversity was calculated using Chao1 index after rarefaction at 8,500 reads per sample and associations addressed using parametric t-test. Principle coordinate analysis was conducted using Bray-Curtis as the beta diversity metric and significance tested using Adonis test. Taxa analysis was completed with Kruskal Wallis test.

Results

263 sigmoid colon biopsies (UC n=101, CD n=96, HC n=48) were analysed. HC showed separation of beta diversity (p<0.001, R<0.15) and greater alpha diversity (0.001<p<0.04) than quiescent CD (n=31), and quiescent UC (n=37) respectively. In HC, taxa analysis identified increased Firmicutes (q=0.001), and reduced Fusobacteria relative abundance (RA) (q=0.04) and at genus level, reduced Actinobacteria microbacteria RA (q<0.04) relative to quiescent UC and CD. We also compared microbiome profiles between IBD phenotypes. In quiescent disease, patients with CD involving the colon clustered with UC patients on a PCoA plot with no significant differences in taxa, however alpha diversity was reduced in CD relative to UC. Patients with endoscopic activity and remission were subsequently combined. CD patients had persistent reduced alpha diversity (p=0.0004), and also weak separation from UC patients by beta diversity metrics (q<0.02, R=0.01). Taxa analysis identified a trend of increased Fusobacteria and Proteobacteria RA (q=0.059), and reduced Coribactericeae adlercreutzia RA in colonic CD compared with UC (q=0.03).

Conclusion

IBD patients have altered microbiome profiles relative to HC in active and quiescent disease, although histological activity was not captured here. Both UC and CD phenotypes had reduced Firmicutes and increased Actinobacteria abundance relative to HC, indicating microbiome dysbiosis in the absence of endoscopic activity. We show reduced alpha diversity in CD phenotypes relative to UC despite no difference in taxa of quiescent patients.