Eicosapentaenoic Acid-Acylated Astaxanthin Ameliorates DSS-Induced Chronic-Like Relapsing Colitis Associated With Gut Microbiota and Bile Acid Metabolism.

Abstract

The role of eicosapentaenoic acid (EPA) in improving ulcerative colitis (UC) has been extensively studied. EPA-acylated astaxanthin (EA), a novel fish oil, has unclear effects on UC. This study constructed a DSS-induced chronic-like relapsing colitis model in mice induced by 2% dextran sulfate sodium (DSS) and primarily concentrated on the changes in gut microbiota and intestinal bile acids (BA) to investigate the anti-UC mechanisms of EA. The results indicated that EA effectively upregulated the expressions of tight junction proteins, ZO-1 and Occludin, while restraining the triggering of the NLRP3 inflammasome. Additionally, EA treatment increased the diversity of the gut microbiota and increased the proportion of Firmicutes, Actinobacteria, and Bifidobacterium, while decreasing the proportion of Bacteroidota, Proteobacteria, and Enterobacteriaceae, which are related to BA metabolism. The metabolomic analysis of BA indicated that EA elevated the concentrations of secondary BA, such as LCA, UDCA, and TUDCA, while decreasing primary BA, such as CA, CDCA, and β-MCA, thereby activating the intestinal ASBT/FXR/TGR5 pathway. In conclusion, EA alleviated DSS-induced colitis, and this protective effect was associated with the modulation of gut microbiota and BA metabolism. The present results laid the foundation for EA as a prospective functional component for UC.