Liver fibrosis is a necessary process for
liver disease. Recent studies have reported that the enterohepatic circulation of
bile acid plays a vital role in developing
liver fibrosis. The Antarctic krill
peptide (AKP) has been proved to have a variety of activities such as
antioxidant and anti-inflammatory, but any possible influence on
liver fibrosis remains unclear. In the current study, the
liver fibrosis mice were
intraperitoneal injection of
carbon tetrachloride (2.5%, 10 mL kg-1) and
oral administration AKP (400 mg kg-1) for 30 days. The results showed that the AKP supplement decreased the serum ALT and AST levels, reduced the content of liver TNF-α and
Collagen I, and improved liver
inflammation and
fibrosis, which was also confirmed by H&E and Masson staining.
Bile acid is an important metabolite for the gut microbiota. We found that the AKP supplement alleviated the gut microbiota
dysbiosis remarkably, as indicated by increased species richness and diversity, and decreased overgrowth of genera Bifidobacterium, Lactobacillus, Bacteroides, Clostridiales and Fusicatenibacter. Furthermore, AKP mediated gut microbiota improvement decreased the intestinal
bile salt hydrolase and 7α-dehydroxylation activities, resulting in the decrease of secondary
bile acid taurodeoxycholic acid (TDCA) and
taurolithocholic acid (TLCA) concentrations. Mechanistically, AKP inhibited NLRP3 signal by downregulating the secondary
bile acid, decreased cleaved Caspase-1 expression to suppress IL-1β-mediated hepatic stellate cell activation. This study reports for the first time that AKP improved
liver fibrosis via improving the gut microbiota mediated bile acid-NLRP3 signaling, which might provide new ideas and evidence for Antarctic krill's high-value utilization.