Exogenous Low-Molecular-Weight Collagen Bioactive Peptides Alleviate Cholestatic Liver Fibrosis in Mice by Modulating CAMs to Inhibit Wnt/β-Catenin Signaling and Restoring Gut Microbiota Homeostasis.

Exogenous low-molecular-weight collagen bioactive peptides (CP) derived from codfish skin have demonstrated anti-inflammatory and antifibrotic effects. However, the roles of CP in protecting against cholestatic liver fibrosis remain unclear. This study aimed to evaluate the effects of CP on cholestatic liver fibrosis. A bile duct ligation (BDL) model was employed, and the effects of CP on liver fibrosis in BDL mice were assessed. Proteomics was used to identify the targets and signaling pathways of the CP. 16S rRNA sequencing was performed to evaluate the effects of CP on the gut microbiota diversity. CP alleviated bile stasis, liver inflammation, oxidative stress, hepatocyte apoptosis, and liver fibrosis. Proteomics and molecular biology revealed that CP targeted cell adhesion molecules (CAMs), thereby inhibiting the Wnt/β-catenin signaling pathway. 16S rRNA sequencing demonstrated that CP restored gut microbiota homeostasis. CP alleviates cholestatic liver fibrosis in mice by modulating CAMs to inhibit Wnt/β-catenin signaling and restore gut microbiota homeostasis.