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<p>Cholestasis, a bile flow disorder common to many liver diseases, currently lacks effective treatments. Emerging evidence links gut microbiota disturbances to cholestatic liver injury. Here, an antibiotic cocktail (ABX)-treated mouse model confirmed the indispensable role of the intestinal microbiota, with marked shifts including increased <i>Alistipes putredinis</i> (<i>A. putredinis</i>) and decreased <i>Clostridium</i> spp. (<i>C</i>. spp.). In vitro, ferulic acid and wogonin effectively modulated the gut flora, and in vivo they alleviated liver injury. Administration of <i>A. putredinis</i> exacerbated hepatic inflammation by disrupting intestinal barrier integrity and facilitating bacterial translocation, an effect reversed by ferulic acid. Conversely, treatment with <i>C. spp</i>. and wogonin enhanced bile salt hydrolase activity and bile acid excretion. Notably, combined treatment with ferulic acid and wogonin or <i>C. spp</i>. significantly ameliorated cholestatic liver injury. These findings underscore the critical role of gut microbiota in cholestasis and suggest therapeutic potential for microbiota-targeted and natural compound-based interventions.</p>

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Synergistic effects of ferulic acid and wogonin on cholestatic liver injury via gut microbiota modulation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月18日

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  • Xin Luo,
  • Ting Mao,
  • Xi Wang,
  • Peng Cheng,
  • Mingyuan Liu,
  • Ruizhi Tao,
  • Feihui Wang,
  • Lizhi Zhao,
  • Yunlong Shan,
  • Yin Lu,
  • Zhonghong Wei

摘要

Cholestasis, a bile flow disorder common to many liver diseases, currently lacks effective treatments. Emerging evidence links gut microbiota disturbances to cholestatic liver injury. Here, an antibiotic cocktail (ABX)-treated mouse model confirmed the indispensable role of the intestinal microbiota, with marked shifts including increased Alistipes putredinis (A. putredinis) and decreased Clostridium spp. (C. spp.). In vitro, ferulic acid and wogonin effectively modulated the gut flora, and in vivo they alleviated liver injury. Administration of A. putredinis exacerbated hepatic inflammation by disrupting intestinal barrier integrity and facilitating bacterial translocation, an effect reversed by ferulic acid. Conversely, treatment with C. spp. and wogonin enhanced bile salt hydrolase activity and bile acid excretion. Notably, combined treatment with ferulic acid and wogonin or C. spp. significantly ameliorated cholestatic liver injury. These findings underscore the critical role of gut microbiota in cholestasis and suggest therapeutic potential for microbiota-targeted and natural compound-based interventions.