Pharmabiotics，Phocaeicola dorei，通过减轻中性粒细胞的巨噬细胞吞噬作用来改善胆汁淤积性肝纤维化
Pharmabiotics, Phocaeicola dorei, ameliorates cholestatic liver fibrosis by alleviating macrophage efferocytosis of neutrophils.
摘要(中文译文)
Phocaeicola dorei据报道可改善代谢性疾病。其在肝纤维化中的作用尚不明确。我们评估了P. dorei在肝纤维化中的肝脏保护作用。收集健康对照者和患者（n=285）的粪便样本，以评估P. dorei的临床相关性。在雄性小鼠模型（3,5-二乙氧羰基-1,4-二氢可力丁[DDC]饮食）中，口服给予P. dorei（10 CFU/g，每周两次）。使用原代肝星状细胞（HSC）、LX-2、THP-1和HL-60细胞系进行机制验证。在人类中，P. dorei的相对丰度随肝病恶化而增加。给予P. dorei可显著减少中性粒细胞脱颗粒和胞葬作用（efferocytosis）通路（Ly6g和F4/80）。中性粒细胞相关趋化因子（Cx3cl1和Cx3cr1）的失调表达经P. dorei处理后得以恢复。P. dorei培养上清液抑制了巨噬细胞介导的胞葬作用。P. dorei通过抑制中性粒细胞和巨噬细胞浸润并破坏胞葬作用来减轻肝纤维化。我们的结果确定P. dorei是胆汁淤积性肝纤维化的一种潜在的基于微生物组的治疗候选物。
Abstract
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 (10 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.
如何引用
AMA
Jung A Eom, In Gyu Park, Ji Ye Hyun, Na Young Lee, Goo Hyun Kwon, Sang Jun Yoon, et al. Pharmabiotics, Phocaeicola dorei, ameliorates cholestatic liver fibrosis by alleviating macrophage efferocytosis of neutrophils.. Nature communications. 2026; doi:10.1038/s41467-026-73166-1.
APA
Jung A Eom, In Gyu Park, Ji Ye Hyun, Na Young Lee, Goo Hyun Kwon, Sang Jun Yoon, et al (2026). Pharmabiotics, Phocaeicola dorei, ameliorates cholestatic liver fibrosis by alleviating macrophage efferocytosis of neutrophils.. Nature communications. https://doi.org/10.1038/s41467-026-73166-1
GB/T 7714
Jung A Eom, In Gyu Park, Ji Ye Hyun, Na Young Lee, Goo Hyun Kwon, Sang Jun Yoon, et al. Pharmabiotics, Phocaeicola dorei, ameliorates cholestatic liver fibrosis by alleviating macrophage efferocytosis of neutrophils.[J]. Nature communications, 2026 doi:10.1038/s41467-026-73166-1.
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