P919 Gut microbial signature and phenotype-specific Indicators in fecal microbiota of Korean patients with Inflammatory Bowel Disease

Abstract Background The incidence and prevalence of inflammatory bowel disease (IBD) in Asian countries have been increasing rapidly over the last few decades. This study was aimed to reveal gut metagenomic characteristics and identify a robust fecal microbial marker in Korean patients with IBD through a large-scale comparative study. Methods Gut metagenomic study using 640 fecal samples collected from patients with 523 IBD (223 Crohn’s disease [CD], 300 ulcerative colitis [UC]) and 117 healthy controls was conducted by 16S rRNA sequencing. Unsupervised cluster analysis based on the predicted functional genes was conducted. Microbiome Multivariable Association with Linear Models was used to determine relationship between metagenomic data and clinical metadata after adjusting for multiple covariates. Results Patients with IBD, particularly CD, had a significantly lower alpha diversity than the controls (p <0.05). An increase in stool consistency was positively associated with community diversity in controls and UC (p = 5.3e-11, Kruskal-Wallis test), but not in patients with CD. Differential abundance analysis revealed an expansion of the phylum Proteobacteria and its constituent taxa in CD, and Ruminococcaceae and Bacteroidaceae families in UC, LDA score [log10] >2.0, p <0.05. Patients with CD had a strong association with Escherichia-Shigella in their fecal microbiome compared to the controls in a multivariable model (FDR <0.01). Microbial functional prediction revealed the strong upregulation of bacterial invasion of epithelial cells and Shigellosis pathways in CD (FDR <0.01, absolute coefficient >2.0). Strong enhancement of the siderophores biosynthesis pathways, the aerobactin and enterobactin biosynthesis pathways (FDR <0.01, absolute coefficient of 2.947 and 1.971, respectively), with abundant contribution from the genus Escherichia-Shigella, is in line with the results obtained from taxonomic profiles. Clustering analysis identified two distinct function-based clusters showing a contrast in the diseae behavior of IBD. Cluster II enriched in patients with stricturing/penetrating Crohn's and extensive UC displayed a significant increase of the genus Escherichia-Shigella (Fig. 1a) and a simultaneous depletion of the genus Faecalibacterium (Fig. 1b), all FDR <10-50. Conclusion The present study adds to the growing evidence that the pathogenesis of CD is underpinned by the genus Escherichia-Shigella. Escherichia-Shigella may be a universal pathobiont in IBD, irrespective of ethnic and life-style backgrounds. Abundance shifting of Escherichia-Shigella and Faecalibacterium in fecal microbiomes is strongly linked with advanced behavior of IBD, which will have significant implications for future research on the diagnosis and treatment of the disease.