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
  • 1. Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China. [email protected].
  • 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. [email protected].
  • 6. Center for Gut Microbiota Research, The Second Hospital of Anhui Medical University, Hefei, Anhui, China. [email protected].
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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