Inulin alleviates HFD-induced NAFLD by hepatic macrophage polarization and lipid metabolism via gut-liver axis

Long-term intake of high-fat diet (HFD) leads to systemic hypo-inflammation, which is involved in the pathogenesis of many liver diseases. The aim of this study was to evaluate the interventional effect of inulin addition on HFD-induced non-alcoholic fatty liver disease (NAFLD). Here, we assessed liver inflammation and lipid metabolism by enzyme linked immunosorbent assay (ELISA) kits and real-time quantitative polymerase chain reaction (qPCR), and explored its relationship with intestinal flora and metabolites by 16S rDNA gene sequencing and untargeted metabolomics. In addition, we determined the effect of the inositol-requiring enzyme-1α-X-box binding protein 1 (IRE1α-XBP1) pathway on liver macrophage polarization by flow cytometry. In conclusion, our study has demonstrated that inulin ameliorates high levels of bile acids and colonic immune disorders induced by HFD, and improves hepatic macrophage polarization and hepatic lipid metabolism via the intestine-hepatic axis, thus providing a mechanistic basis for therapeutic approaches to modulate bile acids to improve colonic inflammation and NAFLD.