Metformin Protects Against Mucus Barrier Dysfunction Via Gut Microbiota In DSS-induced Ulcerative Colitis In Mice

Background and Aims:Metformin has extensive benefits including anti-inflammatory effects.Recent studies showed that metformin changed the composition of gut microbiota and increased the number of goblet cells.Intestinal dysbiosis and goblet cell depletion are important features of ulcerative colitis.Whether metformin can improve mucus barrier in colitis and the underlying mechanism remains unclear.Here we want to determine whether metformin regulate mucus barrier via gut microbiota.Methods:Administration of Metformin(400mg/kg/day)for 2 weeks by oral gavage was performed on Dextran-sulfate-induced UC mice model to investigate the effect of metformin on intestinal mucus barrier.We used antibiotics cocktail to deplete the gut microbiota in mice to explore the its role in the anti-inflammation and mucus-barrier-protected effects of metformin in mice Dextran-sulfate-induced colitis.Results:Metformin attenuated Dextran-sulfate-induced ulcerative colitis in mice,as evidenced by alleviation of diarrhea,hematochezia and the decrease in body weight.The expression of mucin2,the prominent protein of mucus barrier,was increased in metformin-treated group compared to Dextran-sulfate-induced group.And fecal 16S analysis showed that metformin treatment changed gut microbiota composition by increasing the relative abundance of Lactobacillus and Akkermansia while decreasing Erysipelatoclostridium at genus level.The antibiotics treatment abolished the anti-inflammation and mucus-barrier-protected effects of metformin.Conclusions:We concluded that Metformin could alleviate Dextran-sulfate-induced colitis in mice and could be a protective factor for decreasing the extent of goblet cell damage through gut microbiota.