The gut-liver axis mediates the protective effect of Cinnamomum chago polysaccharide against acute liver injury: Insights from integrated microbiome and metabolomics analysis.

Cinnamomum chago B. S. Sun et H. L. Zhao polysaccharide (CCP) was evaluated for its hepatoprotective effects against carbon tetrachloride (CCl₄)-induced acute liver injury (ALI). The results demonstrated that CCP improved liver histopathology in ALI mice, significantly decreased serum biochemical indicators of liver injury, and enhanced hepatic antioxidant capacity. Western blot analysis further revealed that CCP activated the Nrf2/NQO1 signaling pathway, thereby strengthening the antioxidant defense system and alleviating liver damage. Untargeted metabolomics and gut microbiota profiling indicated that CCP increased linoleic acid levels through the biosynthesis of unsaturated fatty acids pathway. The elevated linoleic acid promoted the abundance of Lactobacillus in the gut microbiota, and metabolites produced from their interaction further enhanced systemic antioxidant capacity. Moreover, the CCP-induced increase in linoleic acid activated the hepatic Nrf2 signaling pathway, contributing to the improvement of liver injury. In conclusion, the gut-liver axis plays a crucial protective role in liver health, and the hepatoprotective effects of CCP are mediated by Lactobacillus and linoleic acid through activation of the hepatic Nrf2/NQO1 signaling pathway.