Dose-response framework for DSS-induced colitis in mice.

Dextran sulfate sodium (DSS) is widely used to model epithelial injury-driven colitis, but heterogeneous dosing complicates model selection and cross-study comparison. Here, we established a graded DSS dose-response framework by administering 0%, 1.5%, 2.0%, 2.5%, or 3.0% DSS to C57BL/6J mice for 5 days, followed by 2 days of recovery, and integrated pathological, microbial, transcriptomic, and immune profiling. Low-dose DSS (1.5%-2.0%) induced mild and largely reversible epithelial injury, early microbiota perturbation, and CD8+ T cell accumulation. Higher doses (2.5%-3.0%) caused sustained inflammation, pronounced mucosal damage, macrophage and granulocyte infiltration, and elevated pro-inflammatory cytokines. Transcriptomic analysis revealed shared activation of TNF, NF-κB, IL-17, and NOD-like receptor signaling, with greater amplitude at higher DSS concentrations. This framework supports rational DSS dose selection according to disease severity and experimental objectives.