EGCG drives gut microbial remodeling-induced epithelial GPR43 activation to lessen Th1 polarization in colitis

Siyan Che; Beibei Qin; Kunfu Wu; Mingzhi Zhu; Han Hu; Can Peng; Zi Wang; Yulong Yin; Yaoyao Xia; Miaomiao Wu

Redox Biology (Sep 2024)

EGCG drives gut microbial remodeling-induced epithelial GPR43 activation to lessen Th1 polarization in colitis

Siyan Che,
Beibei Qin,
Kunfu Wu,
Mingzhi Zhu,
Han Hu,
Can Peng,
Zi Wang,
Yulong Yin,
Yaoyao Xia,
Miaomiao Wu

Affiliations

Siyan Che: Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China
Beibei Qin: Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China
Kunfu Wu: Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China
Mingzhi Zhu: Key Laboratory of Tea Science of Ministry of Education, National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha, 410128, China
Han Hu: Institute of Apicultural Research/State Key Laboratory of Resource Insects, Chinese Academy of Agricultural Sciences, Beijing, 100093, China
Can Peng: Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China
Zi Wang: Department of Hematology, The Second Xiangya Hospital of Central South University; Molecular Biology Research Center, Center for Medical Genetics, School of Life Sciences; Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha 410011, China; Corresponding author.
Yulong Yin: Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China; Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China
Yaoyao Xia: College of Animal Science and Technology, Southwest University, Chongqing, 400715, China; Corresponding author.
Miaomiao Wu: Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China; Corresponding author.

Journal volume & issue: Vol. 75
p. 103291

Abstract

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Modulation of immune microenvironment is critical for inflammatory bowel disease (IBD) intervention. Epigallocatechin gallate (EGCG), as a natural low toxicity product, has shown promise in treating IBD. However, whether and how EGCG regulates the intestinal microenvironment is not fully understood. Here we report that EGCG lessens colitis by orchestrating Th1 polarization and self-amplification in a novel manner that required multilevel-regulated intestinal microecosystem. Mechanistically, EGCG activates GPR43 on IEC to inhibit Th1 polarization dependently of short chain fatty acid (SCFA)-producing gut microbiota. Inhibition of GPR43 activity weakens the protective effects of EGCG on colitis development. Moreover, we confirm that fecal SCFAs and/or intestinal GPR43 are limited in patients with colitis and are correlated with Th1 cell number. Taken together, our study reveals an intestinal microenvironment-dependent immunoregulatory effects of EGCG in treating IBD and provides insight into mechanisms of EGCG-based novel immunotherapeutic strategies for IBD.

Published in Redox Biology

ISSN: 2213-2317 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.journals.elsevier.com/redox-biology/

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