P913 Interactions between Intestinal Microbiota and micro-RNAs in Inflammatory Bowel Disease
Eun, C.S.(1)*;Oh, E.H.(1);Lee, A.R.(1);Park, C.H.(1);Han , D.S.(1);
(1)Hanyang University Guri Hospital, Internal Medicine, Guri, Korea- Republic Of;
Background
Both gut microbiota and micro-RNAs (miRNAs) have been implicated in the pathogenesis of inflammatory bowel disease (IBD). We aimed to investigate the interactions between gut microbiota and miRNAs which are altered in murine colitis models and patients with IBD using multi-omics analysis.
Methods
Gut microbiota and miRNAs were analyzed in a mouse experiment (7 dextran sodium sulfate [DSS]-treated mice, 7 azoxymethane [AOM] and DSS-treated mice, and 6 controls) and a human experiment (10 patients with active Crohn’s disease, 10 patients with active ulcerative colitis [UC], and 8 healthy controls). DNA was extracted from mouse feces and human colonic tissues, and 16S rRNA gene sequencing was performed to evaluate changes in gut microbiota. miRNA expression levels were measured by microarray analysis from mouse and human colonic tissues. mRNA expression levels were examined by microarray analysis from colonic tissues of UC patients. Correlation and network analyses were performed to evaluate the interactions among gut microbiota, miRNAs and mRNAs.
Results
Principal coordinate analysis showed distinct gut microbiota composition and miRNA expressions among the groups in the mouse and human experiments. Also, comparative analysis showed many miRNAs differentially expressed and many bacterial amplicon sequence variants (ASVs) differentially identified among the groups. Spearman correlation rank test and network analysis revealed multiple correlations and interactions among specific miRNAs and bacterial ASVs. In UC patients, genes associated with functional categories in biological process, such as positive regulation of cytokine production, cytokine-mediated signaling pathway, cell adhesion, positive regulation of response to external stimulus, and leukocyte migration were upregulated than healthy controls. mRNAs in UC patients also showed multiple correlations and interactions with specific miRNAs and bacterial ASVs.
Conclusion
Gut microbiota composition and miRNA expressions were distinctly altered in patients with IBD and murine colitis models. Specific miRNAs were associated with specific bacterial ASVs and mRNAs, suggesting the interactions among miRNAs, gut microbiota and mRNAs in the pathogenesis of IBD. Our data imply that global complicated interactions between gut microbiota and miRNAs, rather than specific individual microbiota-miRNA interaction, might play more important role in IBD.