Integrated microbiome and metabolomic analyses revealed the antifibrotic effect of vanillic acid on thioacetamide-induced liver fibrosis in mice.

Vanillic acid (VA) is a natural phenolic acid compound that is widely found in various foods and medicinal plants, with a remarkable antifibrotic effect observed in animal studies, but its exact antifibrotic mechanism remains unclear. Herein, hepatic function, fibrotic index, and histopathological, microbiome, and metabolomic methods were used to investigate the potential mechanisms behind the improvement effect of vanillic acid against thioacetamide (TAA)-induced liver fibrosis in mice. Our results showed that VA reversed TAA-induced liver fibrosis manifested a decrease in collagen fiber deposition, serum transaminase, serum hepatic fibrotic index, and liver inflammation indicator levels. When analyzed, TAA injection mainly increased the abundance of Akkermansia and Roseburia and significantly reduced the abundance of Anaerotruncus. VA reversed these changes back to normal levels to varying degrees. Metabolomic profiling demonstrated that VA treatment was efficacious in modulating several key liver metabolites involved in neuroactive ligand-receptor interaction, prolactin signaling pathway, estrogen signaling pathway, and glutathione metabolism. Conclusively, VA may ameliorate liver damage and suppress the fibrogenesis caused by thioacetamide by correcting intestinal microbiota disorders and promoting normal hepatic metabolism. This research provides a novel perspective on vanillic acid as a dietary supplement for hepatic fibrosis improvement.