P1318 Temporal Changes of Gut Microbiota and Micro-RNAs according to Disease Activity in Chronic Colitis

Abstract Background Both gut microbiota and micro-RNAs (miRNAs) have been implicated in the pathogenesis of inflammatory bowel disease. We aimed to investigate the temporal changes and their interactions between gut microbiota and miRNAs according to the disease activity using multi-omics analysis in a murine chronic colitis model. Methods Chronic colitis was induced in the C57BL/6 mice by three rounds of 2.5% DSS exposure. Mice were divided into three groups (n= 8 per group): control group, active group (sacrified at 3 days after the third DSS), and recovery group (sacrificed at 80 days after the third DSS). Clinical activities including weight change and histologic findings of colonic segments were examined. DNA was extracted from mouse feces, and 16S rRNA gene sequencing was performed to evaluate changes in gut microbiota. miRNA expression levels were measured by microarray analysis from mouse colonic tissues. Correlation and network analyses were performed to evaluate the interactions between gut microbiota and miRNAs. Results Alpha diversity indices were increased in the active group compared to control and recovery group. PCoA of metagenomic sequencing showed that the gut microbial profile of the active group was distinctly different from the control group, while the gut microbial profile of the recovery group was similar to the control group. On the other hand, PCoA of miRNA microarray showed that the active group had a significantly different miRNA expression pattern compared to the control group, while the recovery group had a similar miRNA expression pattern to the active group. In taxonomic and miRNA analyses, 147 differential abundant bacterial ASVs and 30 differential expressed miRNAs were identified in the active group compared to the recovery group. Spearman correlation and network analysis between gut microbiota and miRNAs, which showed significant differences between the active and the recovery groups, revealed significant associations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p. Conclusion In the active phase of chronic colitis, the gut microbial composition and miRNA expression were significantly altered, while in the recovery phase of chronic colitis, the gut microbial profile was similar to that of control, but a significantly different miRNA expression pattern was observed. Specific miRNAs were associated with specific bacterial ASVs, suggesting the interactions between miRNAs and gut microbiota in the development of chronic colitis. Our data suggested significant correlations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p in the active phase of chronic colitis.