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

作者：Siyan Che, Beibei Qin, Kunfu Wu, Mingzhi Zhu, Han Hu, Can Peng, Zi Wang, Yulong Yin, Yaoyao Xia, Miaomiao Wu · 发表于：Redox Biology · 年份：2024 · DOI：10.1016/j.redox.2024.103291 · 被引用次数：35 · 研究领域：Gut microbiota and health、Immune Cell Function and Interaction、Dietary Effects on Health

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.