Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice. Here, QKI is linked to inflammatory bowel disease.