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TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway

Background The goal of the present study was to investigate the effects of TAK-242 on the gut microbiota and the TLR4/JAK2/STAT3 signaling pathway in mice with dextran sulfate sodium (DSS)-induced… Click to show full abstract

Background The goal of the present study was to investigate the effects of TAK-242 on the gut microbiota and the TLR4/JAK2/STAT3 signaling pathway in mice with dextran sulfate sodium (DSS)-induced colitis. Results At the phylum level, Bacteroidetes , Firmicutes , Actinobacteria , Cyanobacteria , Epsilonbacteraeota and Proteobacteria were the primary microbiota in the five groups. TAK-242 treatment significantly enhanced Verrucomicrobia and Actinobacteria ; significantly decreased Cyanobacteria, Epsilonbacteraeota and Proteobacteria ; and particularly promoted the growth of Akkermansia . TAK-242 markedly alleviated DSS-induced colitis symptoms and colonic lesions by promoting IL-10 release, inhibiting IL-17 release, downregulating TLR4 and JAK2/STAT3 mRNA and protein expression and increasing JAK2/STAT3 phosphorylation. Conclusion TAK-242 modulates the structure of the gut microbiota in colitis and may be a novel therapeutic candidate for ulcerative colitis.

Keywords: colitis; jak2 stat3; tak 242; gut microbiota

Journal Title: Microbial Cell Factories
Year Published: 2020

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