In the present research, we investigated the effect of TAK-242 on dextran sulfate sodium (DSS)-induced colitis and analyzed the crosstalk of the gut microbiota and the JAK2/STAT3 signaling pathways to explore whether the TLR4 inhibitor TAK-242 could act as a potential therapeutic option for UC and possible crosstalk mechanism between the gut microbiota and the host. The gene discussed is TLR4; the disease is colitis.