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 colitis. RESULTS: At the phylum level, Bacteroidetes, Firmicutes, Actinobacteria, Cyanobacteria, Epsil...

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Autores principales: Wang, Jiajia, Zhu, Guannan, Sun, Cheng, Xiong, Kangwei, Yao, Tingting, Su, Yuan, Fang, Haiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412642/
https://www.ncbi.nlm.nih.gov/pubmed/32762699
http://dx.doi.org/10.1186/s12934-020-01417-x
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author Wang, Jiajia
Zhu, Guannan
Sun, Cheng
Xiong, Kangwei
Yao, Tingting
Su, Yuan
Fang, Haiming
author_facet Wang, Jiajia
Zhu, Guannan
Sun, Cheng
Xiong, Kangwei
Yao, Tingting
Su, Yuan
Fang, Haiming
author_sort Wang, Jiajia
collection PubMed
description 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.
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spelling pubmed-74126422020-08-10 TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway Wang, Jiajia Zhu, Guannan Sun, Cheng Xiong, Kangwei Yao, Tingting Su, Yuan Fang, Haiming Microb Cell Fact Research 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. BioMed Central 2020-08-06 /pmc/articles/PMC7412642/ /pubmed/32762699 http://dx.doi.org/10.1186/s12934-020-01417-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wang, Jiajia
Zhu, Guannan
Sun, Cheng
Xiong, Kangwei
Yao, Tingting
Su, Yuan
Fang, Haiming
TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway
title TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway
title_full TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway
title_fullStr TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway
title_full_unstemmed TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway
title_short TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway
title_sort tak-242 ameliorates dss-induced colitis by regulating the gut microbiota and the jak2/stat3 signaling pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412642/
https://www.ncbi.nlm.nih.gov/pubmed/32762699
http://dx.doi.org/10.1186/s12934-020-01417-x
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