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.

中文翻译：

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EGCG 驱动肠道微生物重塑诱导的上皮 GPR43 激活，减少结肠炎中的 Th1 极化


免疫微环境的调节对于炎症性肠病（IBD）干预至关重要。表没食子儿茶素没食子酸酯（EGCG）作为一种天然低毒产品，在治疗IBD方面显示出良好的前景。然而，EGCG是否以及如何调节肠道微环境尚不完全清楚。在此，我们报道 EGCG 通过以一种需要多级调节肠道微生态系统的新颖方式协调 Th1 极化和自我扩增来减轻结肠炎。从机制上讲，EGCG 激活 IEC 上的 GPR43，以抑制依赖于产生短链脂肪酸 (SCFA) 的肠道微生物群的 Th1 极化。抑制 GPR43 活性会削弱 EGCG 对结肠炎发展的保护作用。此外，我们证实粪便 SCFA 和/或肠道 GPR43 在结肠炎患者中有限，并且与 Th1 细胞数量相关。综上所述，我们的研究揭示了 EGCG 在治疗 IBD 中的肠道微环境依赖性免疫调节作用，并深入了解基于 EGCG 的 IBD 新型免疫治疗策略的机制。