AUTHOR=Zhou Luping , Zeng Xiangchang , Liao Jianwei , Chen Lulu , Ouyang Dongsheng 

TITLE=Gut Microbiota Modulates the Protective Role of Ginsenoside Compound K Against Sodium Valproate-Induced Hepatotoxicity in Rat

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.936585

DOI=10.3389/fmicb.2022.936585

ISSN=1664-302X

ABSTRACT=<p>This study aimed to investigate the potential role of gut microbiota in the hepatotoxicity of sodium valproate (SVP) and the protective effect of ginsenoside compound K (G-CK) administration against SVP-induced hepatotoxicity in rats. Measurements of 16S rRNA showed that SVP supplementation led to a 140.749- and 248.900-fold increase in the relative abundance of <italic>Akkermansia muciniphila</italic> (<italic>A. muciniphila</italic>) and <italic>Bifidobacterium pseudolongum</italic> (<italic>B. pseudolongum</italic>), respectively (<italic>p</italic> &lt; 0.05). The increase in <italic>A. muciniphila</italic> was almost completely reversed by G-CK treatment. The relative abundance of <italic>A. muciniphila</italic> was strongly positively correlated with aspartate transaminase (AST) and alanine aminotransferase (ALT) levels (<italic>r</italic> &gt; 0.78, <italic>p</italic> &lt; 0.05). The PICRUSt analysis showed that G-CK could inhibit the changes of seven pathways caused by SVP, of which four pathways, including the fatty acid biosynthesis, lipid biosynthesis, glycolysis/gluconeogenesis, and pyruvate metabolism, were found to be negatively correlated with AST and ALT levels (<italic>r</italic> ≥ 0.70, <italic>p</italic> &lt; 0.01 or &lt; 0.05). In addition, the glycolysis/gluconeogenesis and pyruvate metabolism were negatively correlated with the relative abundance of <italic>A. muciniphila</italic> (<italic>r</italic> &gt; 0.65, <italic>p</italic> &lt; 0.01 or &lt; 0.05). This alteration of the gut microbiota composition that resulted in observed changes to the glycolysis/gluconeogenesis and pyruvate metabolism may be involved in both the hepatotoxicity of SVP and the protective effect of G-CK administration against SVP-induced hepatotoxicity. Our study provides new evidence linking the gut microbiota with SVP-induced hepatotoxicity.</p>