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Metl is a newly identified secreted protein highly expressed in the intestinal epithelium.This study aimed to explore the role and mechanism of intestinal epithelial Metl in ulcerative colitis.Metl-/-(intestinal epithelial cell-specific Metl knockout) mice did not display any phenotypes of colitis under basal conditions.However,under administration of 3％ dextran sodium sulfate (DSS)drinking water,colitis was more severe in Metl-/-mice than in WT mice,as indicated by comparisons of body weight loss,the presence of occult or gross blood per rectum,stool consistency,shrinkage in the colon,intestinal damage,and serum levels of inflammatory factors.DSS-induced colitis activated autophagy in the colon.This activation was partially inhibited by intestinal epithelial Metl deficiency,as indicated by a decrease in Beclin-1 and LC3-Ⅱ/Ⅰ and an increase in p62 in DSS-treated Metl-/-mice compared with WT mice.These phenomena were further confirmed by observation of autophagosomes and immunofluorescence staining for LC3 in epithelial cells.The autophagy-related AMPK-mTOR-p70S6K pathway was also activated in DSS-induced colitis,and this pathway was partially blocked by intestinal epithelial Metl deficiency,as indicated by a decrease in AMPK phosphorylation and an increase in mTOR and p70S6K phosphorylation in DSS-treated Metl-/-mice compared with WT mice.Therefore,Metl deficiency deteriorated ulcerative colitis at least partially through inhibition of autophagy via the AMPK-mTOR-p70S6K pathway,suggesting that Metl is a therapeutic target for ulcerative colitis.