Deficiency of miRNA-149-3p shaped gut microbiota and enhanced dextran sulfate sodium-induced colitis

Abstract

Genetic predisposition and disruption of host gut microbiota and immune system can result in inflammatory bowel disease (IBD). Here, we show that miRNA-149-5p (miR-149-5p) and miRNA-149-3p (miR-149-3p) play crucial roles in IBD. Mice lacking miR-149-3p were considerably more susceptible to dextran sulfate sodium (DSS)-induced colitis than wild-type (WT) mice, accompanied by more serious inflammatory symptoms and increased gene expression of certain inflammatory cytokines. Both miR-149-5p and miR-149-3p suppressed colon inflammatory response in vitro and in vivo. Furthermore, we found significant differences in the composition of the gut microbiota between WT and miR-149-3p−/− mice by 16S rRNA sequencing. Co-housing endowed susceptibility to WT mice against DSS-induced colitis compared with the WT control group. However, susceptibility of miR-149-3p−/− mice against DSS-induced colitis was still present after antibiotic treatment. These findings suggest that the deletion of miR-149-3p altered gut microbiota and influenced pathogenesis of intestinal inflammation, but sensitivity of miR-149-3p−/− mice to DSS-induced colitis is not conferred by microbiota. In addition, we identified the roles of miR-149-5p and miR-149-3p in colon inflammation, which may serve as an attractive therapeutic tool for colitis or IBD, and even colitis-associated carcinoma.

Keywords

• MT: Non-coding RNAs
• miR-149-3p
• miR-149-5p
• colitis
• IBD
• gut microbiota