Here, we first confirmed that DSS increased the expression of pro-inflammatory cytokines TNF-α (Tnf), Il1β, and Ifng, led to gut microbiota dysbiosis, and skewed immune responses in MLNs and the circulation, which in turn could increase intestinal permeability and bacterial translocation, consequently resulting in profound intestinal damage and colitis in young mice. Here, IFNG is linked to colitis.