Therapeutic modulation of miRNA expression by Bifidobacterium bifidum in a DSS-induced colitis mouse model

The regulatory interplay between the gut microbiome and microRNAs (miRNAs) in modulating inflammation is increasingly recognized, particularly in diseases such as inflammatory bowel disease (IBD). This study evaluated the therapeutic effects of B. bifidum on DSS-induced colitis in mice, focusing on the modulation of miR-125 and miR-103 expression. In the current study, 30 male C57BL/6 mice using a computer-generated randomization sequence were assigned to the five experimental groups as healthy control (HC), disease model (DM), pre-and co-treatment (Pre-Co-Bb), pre-treatment (Pre-Bb), and post-treatment (Post-Bb) with B. bifidum (2 × 10 9 CFU/day). IBD progression was evaluated through disease activity index (DAI), histopathological analysis, inflammatory cytokines including interleukin-6 (IL-6) and tumor-necrosis-factor-α (TNF-α), and gene expression of CCL8, p38, miR-125, and miR-103 variants using RT-PCR. B. bifidum treatment significantly alleviated colitis symptoms across all treatment groups ( P < 0.05), with the Post-Bb group demonstrating the most pronounced therapeutic effects, including restored colon length, reduced inflammatory markers, and improved mucosal architecture. The DM group exhibited a substantial upregulation of miR-125 and miR-103 compared to healthy controls, with miR-125a and miR-125b demonstrating significantly increased fold changes. Treatment with B. bifidum significantly downregulated these miRNAs across all groups, with the Post-Bb group showing the strongest reductions ( P < 0.0001). For miR-103 variants, similar patterns were observed ( P < 0.0001). Post-Bb treatment effectively modulated miRNA expression, showing significant reductions in IL-6 and TNF-α, p38, miR-125, and miR-103 levels and a considerable increase in CCL8 gene expression level ( p < 0.05). These findings demonstrate that B. bifidum alleviates DSS-induced intestinal inflammation and is associated with modulation of miR-125, miR-103, and inflammatory mediators. These results support the potential therapeutic value of B. bifidum in experimental colitis.