Genistein alleviates dextran sulfate sodium-induced colitis in mice through modulation of intestinal microbiota and macrophage polarization.

Abstract

Ulcerative colitis (UC) is a colonic immune system disorder, manifested with long duration and easy relapse. Genistein has been reported to possess various biological activities. However, it remains unclear whether genistein can ameliorate UC by modulating the homeostasis of the intestinal bacterial community. The dextran sodium sulfate (DSS)-induced UC mice were administrated with genistein (20mg/kg/day) or genistein (40mg/kg/day) for ten days. The general physical condition of the mice was monitored. After sacrifice, the changes in colon length and colonic pathological morphology were observed. The expression of intestinal barrier proteins, inflammatory cytokines, and macrophage markers in the colon was detected. The composition and metabolic products of the intestinal microbiota were analyzed. Genistein treatment visibly improved body weight change and disease activity index in DSS-induced mice. Genistein treatment ameliorated colonic pathological alterations and promoted the expression of mucin-2 and tight junction proteins. Genistein administration inhibited myeloperoxidase activity and colonic inflammatory cytokines. Furthermore, genistein administration improved the structure of the intestinal microbial community, promoted the production of short-chain fatty acids, and modulated macrophage polarization. These results revealed that genistein mediated macrophage polarization balance by improving intestinal microbiota and its metabolites, thereby alleviating DSS-induced colitis.