Crocin Supplementation Mitigates <scp>DSS</scp> ‐Induced Ulcerative Colitis by Promoting Autophagy and Modulating Gut Microbiota in Mice

ABSTRACT Crocin has been widely recognized for its anti‐inflammatory and antioxidant properties. The study aimed to explore the pharmacological effects and underlying mechanism of crocin in treating ulcerative colitis (UC) induced by a 3% dextran sulfate sodium (DSS). Results showed that crocin supplementation attenuated diarrhea and hematochezia, as well as mitigated splenomegaly and colon shortening in DSS‐induced UC mice. Histopathological analysis demonstrated that crocin supplementation suppressed DSS‐induced inflammatory infiltration and mucosal damage, accompanied by an increase in the number of goblet cells and an elevated expression of mucin‐2. Furthermore, crocin supplementation enhanced gut barrier integrity by increasing the expression of tight junction proteins and inhibited intestinal inflammation by targeting the nucleotide‐binding domain‐like receptors family pyrin domain containing 3 inflammasome signaling pathway. This protective mechanism may be attributed to crocin's ability to enhance autophagy by regulating the AMP‐activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway, accompanied by the upregulation of autophagy‐related proteins. Additionally, crocin appears to alter gut microbiota compositions, characterized by a reduction in the relative abundance of Proteobacteria and an increase in Akkermansia abundance. Our findings provide experimental evidence that crocin alleviates DSS‐induced colitis by activating autophagy and reshaping the gut microbiota, concurrently enhancing gut barrier function and inhibiting intestinal inflammation. Crocin may be an effective nutritional intervention strategy for future UC prevention and treatment in patients.