NFE2L2 and neoplasm: This review systematically examines three fundamental regulatory mechanisms through which gut microbiota and its metabolites mitigate radiation-induced injury: (1) modulation of intestinal epithelial cell regeneration and tumor cell apoptosis via Wnt/β-catenin and PI3K/AKT/mTOR pathways; (2) immunomodulation via Toll-like receptor activation and NF-κB signaling; (3) oxidative stress management via Nrf2 signaling.