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<p><i>Phocaeicola dorei</i> has been reported to ameliorate metabolic diseases. Its role in liver fibrosis remains unclear. We evaluated the hepatoprotective effect of <i>P. dorei</i> in liver fibrosis. Fecal samples were collected from healthy controls and patients (<i>n</i> = 285) to assess the clinical relevance of <i>P. dorei</i>. In male mice models (3,5-diethoxycarbonyl-1.4-dihydrocollidine [DDC] diet), <i>P. dorei</i> (10<sup>9</sup> CFU/g twice/week) was orally administered. Primary HSCs, LX-2, THP-1, and HL-60 cell lines were used for mechanical validation. The relative abundance of <i>P. dorei</i> increased with worsing liver disease in human. <i>P. dorei</i> administration significantly reduced neutrophil degranulation and efferocytosis pathways (<i>Ly6g</i> and <i>F4/80</i>). The dysregulated expression of neutrophil-associated chemokines (<i>Cx3cl1</i> and <i>Cx3cr1)</i> was restored by <i>P. dorei</i>. <i>P. dorei</i> culture supernatant inhibited macrophage-mediated efferocytosis<i>. P. dorei</i> attenuates liver fibrosis by suppressing neutrophil and macrophage infiltration and disrupting efferocytosis. Our results identify <i>P. dorei</i> as a potential microbiome-based therapeutic candidate for cholestatic liver fibrosis.</p>

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Pharmabiotics, Phocaeicola dorei, ameliorates cholestatic liver fibrosis by alleviating macrophage efferocytosis of neutrophils

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月17日

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  • Jung A Eom,
  • In Gyu Park,
  • Ji Ye Hyun,
  • Na Young Lee,
  • Goo Hyun Kwon,
  • Sang Jun Yoon,
  • Sung-Min Won,
  • Young Lim Ham,
  • Kyeong Jin Lee,
  • Sang Hak Han,
  • Dong-Hoon Yang,
  • Dong Joon Kim,
  • Ki Tae Suk

摘要

Phocaeicola dorei has been reported to ameliorate metabolic diseases. Its role in liver fibrosis remains unclear. We evaluated the hepatoprotective effect of P. dorei in liver fibrosis. Fecal samples were collected from healthy controls and patients (n = 285) to assess the clinical relevance of P. dorei. In male mice models (3,5-diethoxycarbonyl-1.4-dihydrocollidine [DDC] diet), P. dorei (109 CFU/g twice/week) was orally administered. Primary HSCs, LX-2, THP-1, and HL-60 cell lines were used for mechanical validation. The relative abundance of P. dorei increased with worsing liver disease in human. P. dorei administration significantly reduced neutrophil degranulation and efferocytosis pathways (Ly6g and F4/80). The dysregulated expression of neutrophil-associated chemokines (Cx3cl1 and Cx3cr1) was restored by P. dorei. P. dorei culture supernatant inhibited macrophage-mediated efferocytosis. P. dorei attenuates liver fibrosis by suppressing neutrophil and macrophage infiltration and disrupting efferocytosis. Our results identify P. dorei as a potential microbiome-based therapeutic candidate for cholestatic liver fibrosis.