Vanillic acid reverses liver fibrosis in Thioacetamide-induced mice by regulating gut microbiota disorders, amino acid and estrogen metabolism
Vanillic acid (VA) is an aromatic phenolic acid widely present in food, which has hepatoprotective activity. The aim of this study was to investigate the effects of VA on fecal microbiota and liver metabolism in mice with liver fibrosis. After 8 weeks of Thioacetamide (TAA) injection, collagen fiber deposition occurred in the liver of mice, and liver fibrosis related indicators were significantly increased. The above symptoms were relieved after high-dose vanillic acid (VAH) treatment. The results of intestinal microbiota showed vanillic acid reversed the imbalance of intestinal microbiota induced by TAA and restored a series of microbiota represented by Akkermansia to normal levels. Further liver metabolomics results showed that the TAA group increased in Estradiol, gamma-aminobutyric acid, and L-serine. Moreover, compared with the TAA group, these metabolites were significantly reduced and 15(S)-HPETE, Saccharopine and other metabolites were increased in the VAH group. The change of metabolites indicated that high-dose VA could change the metabolism pattern of gonadotropin and amino acid metabolism, besides inhibiting the progression of fibrosis in mice. We conclude that VA can correct intestinal microbiota disorder, promote the normal metabolism of sex hormones and amino acids, and play a pharmacological role in inhibiting liver fibrosis.