Given the nascent stage of mechanistic research, we utilized DSS‐induced colitis in C57BL/6 mice to systematically evaluate: (1) DM's disease‐modifying effects (Disease Activity Index [DAI], histology, colon length), (2) mucosal barrier restoration (ZO‐1, occludin, MUC2 expression), (3) TLR4/NF‐κB pathway modulation, and (4) microbiota restructuring (16S rRNA sequencing). Here, MUC2 is linked to colitis.