Activation of a Specific Gut Bacteroides-Folate-Liver Axis Benefits for the Alleviation of Nonalcoholic Hepatic Steatosis
Activation of a Specific Gut Bacteroides-Folate-Liver Axis Benefits for the Alleviation of Nonalcoholic Hepatic Steatosis
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DOI：
10.1016/j.celrep.2020.108005
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发表时间：
2020-08-11
期刊：
影响因子：
8.8
通讯作者：
Liu, Hongwei
中科院分区：
文献类型：
--
作者：
Qiao, Shanshan;Bao, Li;Liu, Hongwei
一个有益的肠道类杆菌-叶酸-肝脏途径调节脂质代谢被证明。口服灵芝部分萜衍生物（GMD）通过减少内毒素血症、增强脂质氧化、减少从头脂肪生成和抑制脂质从肝脏输出来改善fa/fa大鼠肝脏中的非酒精性肝脂肪变性。丁酸盐和叶酸盐增加的改变的肠道微生物群在GMD的作用中起着致病作用。由GMD富集的肠道细菌木聚糖分解拟杆菌、多形拟杆菌、多雷拟杆菌和单形拟杆菌是增加的肠道叶酸盐的主要贡献者。给予live B。在小鼠中，木聚糖溶剂化物减少肝脂肪变性并增强叶酸介导的信号传导途径。B中叶酸生物合成folp基因的敲除。木聚糖溶剂化物阻断其叶酸的产生和有益作用。这项工作证实了GMD和B的治疗潜力。木聚糖溶剂化物在缓解非酒精性肝脂肪变性中的作用，并为肠道类杆菌-叶酸-肝脏途径的益处提供了证据。
A beneficial gut Bacteroides-folate-liver pathway regulating lipid metabolism is demonstrated. Oral administration of a Ganoderma meroterpene derivative (GMD) ameliorates nonalcoholic hepatic steatosis in the liver of fa/fa rats by reducing endotoxemia, enhancing lipid oxidation, decreasing de novo lipogenesis, and suppressing lipid export from the liver. An altered gut microbiota with an increase of butyrate and folate plays a causative role in the effects of GMD, The commensal bacteria Bacteroides xylanisolvens, Bacteroides thetaiotaomicron, Bacteroides dorei, and Bacteroides uniformis, which are enriched by GMD, are major contributors to the increased gut folate. Administration of live B. xylanisolvens reduces hepatic steatosis and enhances the folate-mediated signaling pathways in mice. Knockout of the folate biosynthetic folp gene in B. xylanisolvens blocks its folate production and beneficial effects. This work confirms the therapeutic potential of GMD and B. xylanisolvens in alleviating nonalcoholic hepatic steatosis and provides evidence for benefits of the gut Bacteroides-folate-liver pathway.