Multiomics Dissection of the Mechanisms Underlying Eicosapentaenoic Acid Astaxanthin Ester-Mediated Protection Against High-Fat Diet-Induced Gut Barrier Injury

Abstract

The intestinal barrier proves exquisitely sensitive to dietary cues and is intimately linked to the progression of intestinal, metabolic, and systemic disorders. This study explored the effects of eicosapentaenoic acid astaxanthin ester (EA) on high-fat-diet (HFD)-induced intestinal barrier damage based on the modification of gut microecology. The results showed that EA inhibited obesity development, dyslipidemia, and colon inflammation, suppressed colon pathological damage, and restored the intestinal barrier by upregulating ZO-1 and Occludin, but these improvement effects were lost in pseudogerm-free mice. 16S rRNA sequencing revealed that EA reconfigured the dysbiotic microbiome and selectively expanded barrier-protective genera such as Akkermansia, Muribaculum, Parabacteroides, and Lactobacillus. Transcriptomic analysis indicated that EA regulated cholesterol metabolism and bile secretion. Moreover, EA increased the levels of total bile acids (BAs), secondary BAs, and unconjugated BAs, and the upregulated BAs activated the intestinal farnesoid X receptor. Collectively, these findings provided novel evidence that EA alleviated HFD-induced gut barrier injury.