EGCG ameliorates DSS-induced colitis potentially via suppressing GPR43-mediated Th1 polarization

Abstract Epigallocatechin gallate (EGCG) from green tea has efficacy in preventing progression and alleviating severity of inflammatory diseases, including colitis. However, the protective mechanisms exerted by EGEC are unclear. We hypothesize that reciprocal interactions between intestinal microbiota and immune cells contributes to this protection. Here, we showed that EGCG-alleviated colitis development was associated with suppressed Th1 cell polarization. Moreover, we showed that the mild phenotype observed in EGCG-treated mice correlates with increased SCFAs-producing bacteria enrichment, suggesting the involvement of intestinal microbiota in EGCG-mediated colitis protection. Through molecular docking and molecular dynamic simulation, we found an interaction of EGCG and GPR43, a critical SCFA receptor. Furthermore, EGCG-induced alleviation involved inhibition of Th1 cell differentiation through IκB/NFκB signal pathways. Importantly, EGCG treatment reduced Il12b, Il12rb, Stat4, and Ifng levels, and decreased IL12 levels in colitis mice. Thus, EGCG showed protective action in experimental colitis mice acting through EGCG/GPR43/NFκB/IL-12 pathway, which provides a novel strategy and target for UC prevention targeting immune microenvironment modulation as well as microbial remodeling.