2. Academic Validation
  3. TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway

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

  • Microb Cell Fact. 2020 Aug 6;19(1):158. doi: 10.1186/s12934-020-01417-x.
Jiajia Wang 1,  Guannan Zhu 2,  Cheng Sun 2,  Kangwei Xiong 3 4,  Tingting Yao 3 4,  Yuan Su 3 4,  Haiming Fang 5 6
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China. wjj@ahmu.edu.cn.
  • 2 Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.
  • 3 Department of Gastroenterology and Hepatology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China.
  • 4 Center for Gut Microbiota Research, The Second Hospital of Anhui Medical University, Hefei, Anhui, China.
  • 5 Department of Gastroenterology and Hepatology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China. haimingfang@ahmu.edu.cn.
  • 6 Center for Gut Microbiota Research, The Second Hospital of Anhui Medical University, Hefei, Anhui, China. haimingfang@ahmu.edu.cn.
PMID: 32762699 DOI: 10.1186/s12934-020-01417-x
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

Gut microbiota; Inflammatory bowel disease; JAK/STAT signaling pathway; TAK-242; TLR-4; Ulcerative colitis.

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