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.
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.
