EGCG alleviates colitis in inflammatory bowel disease via gut microbiota-derived LCA and inhibition of NLRP3 inflammasome.

Abstract

The incidence of inflammatory bowel disease (IBD) is increasing worldwide and has caused an enormous economic burden. As the main polyphenolic bioactive substance in green tea, epigallocatechin-3-gallate (EGCG) exerts anti-inflammatory and antioxidant effects. In this study, we explore the potential mechanism by which EGCG relieves experimental colitis by regulating gut microbiota. It revealed colon inflammation in mice was alleviated after oral EGCG treatment. In addition, 16S-rRNA and UHPLC-MS/MS analysis showed that EGCG reversed the microbiota imbalance of colitis mice, enriched BA synthesis pathway Ko00121, and increased the abundance of BA synthase and lithocholic acid (LCA). After administering LCA treatment to mice with colitis, it was observed that LCA exhibited a comparable effect to EGCG in alleviating colitis symptoms. Furthermore, EGCG not only inhibited the polarization of M1 macrophages, but also inhibited the secretion of the proinflammatory factors Caspase-1 and IL-1β, which limited the level of intestinal inflammation and protected intestinal epithelial cells. Our investigation underscores the therapeutic potential of epigallocatechin gallate (EGCG) in colitis, as it exerts anti-inflammatory effects through the reprogramming of gut microbiota and bile acid (BA) metabolism. This discovery offers a novel perspective and strategy for the management of IBD.