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.
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.
Redox Biol. 2024 Sep;75:103291. doi: 10.1016/j.redox.2024.103291. Epub 2024 Jul 30.
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.
调控免疫微环境对于炎症性肠病（IBD）的干预至关重要。表没食子儿茶素没食子酸酯（EGCG）作为一种天然低毒性产物，在治疗 IBD 方面显示出了良好的前景。然而，EGCG 是否以及如何调节肠道微环境尚不完全清楚。在这里，我们报告 EGCG 通过一种新颖的方式减轻结肠炎，这种方式需要多层次调节肠道微生态系统来协调 Th1 极化和自我放大。在机制上，EGCG 通过抑制产生短链脂肪酸（SCFA）的肠道微生物群来激活 IEC 上的 GPR43，从而独立于 SCFA 抑制 Th1 极化。抑制 GPR43 的活性会减弱 EGCG 对结肠炎发展的保护作用。此外，我们证实，粪便 SCFAs 和/或肠道 GPR43 在结肠炎患者中受到限制，并且与 Th1 细胞数量相关。总之，我们的研究揭示了 EGCG 在治疗 IBD 中的一种肠道微环境依赖性免疫调节作用，并为基于 EGCG 的新型免疫治疗策略提供了对 IBD 发病机制的深入了解。
