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IntroductionUlcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent and remitting inflammation of the mucosa of the colon and rectum, the incidence of which is on the rise. Glucagon-like peptide-2 (GLP-2) is a newly discovered neurotrophic factor, but its efficacy and mechanism of action in UC remain unclear. In this study, we investigated the protective effects and potential targets of GLP-2 on dextran sodium sulfate (DSS)-induced UC in mice through integrative analysis.MethodsThe effects of GLP-2 on UC were assessed by calculating the disease activity index, colonic mucosal damage index, and pathological histological scores. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the expression of GLP-2, nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3). The 16SrRNA gene was used to detect changes in gut microbiota in mouse colonic tissues, and oral glucose tolerance test (OGTT) blood glucose levels were used to analyze the differences in flora.ResultsThe results showed that GLP-2 could reduce the inflammation of UC mice, which may be achieved by inhibiting the potential targets of NF-κB, and Janus kinase (JAK)/STAT3 inflammatory pathways, regulating sugar metabolism, increasing dominant species, and improving microbial diversity.DiscussionThis study provides new insight into the potential of GLP-2 for achieving more ideal UC treatment goals in future.

Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurrence and remission of colonic and rectal mucosal inflammation, and its incidence is increasing year by year. Glucagon-like peptide-2 (GLP-2) is a newly discovered enteral nutrition factor, but its efficacy and potential mechanism of action on UC have not been fully elucidated. Aims The purpose of this study was to investigate the protective effect of GLP-2 on Dextran sulfate sodium (DSS) -induced UC in mice and its potential mechanism. Methods 40 C57BL/6J female mice were randomly divided into 4 groups: control group (CON) ,DSS group (DSS) ,DSS + Enterotoxigenic Escherichia coli group (ETEC) ,DSS + ETEC + sitagliptin group (GLP-2). The effect of GLP-2 on UC was evaluated by calculating the disease activity index (DAI), colonic mucosal damage index (CMDI), and histopathological score. The expressions of GLP-2, nuclear factor κB (NF-κB), Interleukin-6 (IL-6), and signal transducer and activator of transcription 3 (STAT3) were detected by the Enzyme-Linked Immunosorbent Assay (ELISA ) and immunohistochemistry. 16SrRNA was used to detect the changes in gut microbiota in mouse colonic tissue. Results Compared with the control group, the GLP-2 of mice in the DSS group and ETEC group decreased significantly, and NF-κB, IL-6, and STAT3 were significantly increased(P < 0.0001). Compared with the DSS group, the CMDI score and histopathological score of the GLP-2 group were significantly decreased, GLP-2 expression was significantly increased, and NF-κB, IL-6, and STAT3 were significantly decreased. The results of 16SrRNA detection showed that compared with the DSS group, the dominant bacteria such as Lactobacillus and Prevotellaceae were increased and the diversity of gut microbiota was increased in the GLP-2 group. Conclusions GLP-2 reduced the degree of inflammation in UC mice, which may be achieved by inhibiting the inflammatory pathways of NF-κB and Janus Kinase (JAK) /STAT3, increasing the dominant bacteria and improving the diversity of gut microbiota.