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Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages.
Cell Reports ( IF 7.5 ) Pub Date : 2018-Apr-24 , DOI: 10.1016/j.celrep.2018.03.109 Smitha Krishnan 1 , Yufang Ding 2 , Nima Saedi 3 , Maria Choi 1 , Gautham V Sridharan 1 , David H Sherr 4 , Martin L Yarmush 3 , Robert C Alaniz 5 , Arul Jayaraman 6 , Kyongbum Lee 1
Cell Reports ( IF 7.5 ) Pub Date : 2018-Apr-24 , DOI: 10.1016/j.celrep.2018.03.109 Smitha Krishnan 1 , Yufang Ding 2 , Nima Saedi 3 , Maria Choi 1 , Gautham V Sridharan 1 , David H Sherr 4 , Martin L Yarmush 3 , Robert C Alaniz 5 , Arul Jayaraman 6 , Kyongbum Lee 1
Affiliation
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The gut microbiota plays a significant role in the progression of fatty liver disease; however, the mediators and their mechanisms remain to be elucidated. Comparing metabolite profile differences between germ-free and conventionally raised mice against differences between mice fed a low- and high-fat diet (HFD), we identified tryptamine and indole-3-acetate (I3A) as metabolites that depend on the microbiota and are depleted under a HFD. Both metabolites reduced fatty-acid- and LPS-stimulated production of pro-inflammatory cytokines in macrophages and inhibited the migration of cells toward a chemokine, with I3A exhibiting greater potency. In hepatocytes, I3A attenuated inflammatory responses under lipid loading and reduced the expression of fatty acid synthase and sterol regulatory element-binding protein-1c. These effects were abrogated in the presence of an aryl-hydrocarbon receptor (AhR) antagonist, indicating that the effects are AhR dependent. Our results suggest that gut microbiota could influence inflammatory responses in the liver through metabolites engaging host receptors.
中文翻译：
肠道菌群衍生的色氨酸代谢产物可调节肝细胞和巨噬细胞的炎症反应。
肠道菌群在脂肪肝疾病的进展中起着重要作用。然而，调解人及其机制尚待阐明。比较无菌和常规饲养的小鼠与低脂和高脂饮食（HFD）的小鼠之间的代谢物差异，我们鉴定出色胺和3型吲哚乙酸酯（I3A）是取决于微生物群的代谢物，并且在HFD下耗尽。两种代谢物均减少了巨噬细胞中脂肪酸和LPS刺激的促炎性细胞因子的产生，并抑制了细胞向趋化因子的迁移，I3A表现出更大的效价。在肝细胞中，I3A减轻了脂质负荷下的炎症反应，并降低了脂肪酸合酶和固醇调节元件结合蛋白1c的表达。在存在芳基碳氢化合物受体（AhR）拮抗剂的情况下，这些作用被取消，表明该作用是AhR依赖性的。我们的结果表明，肠道菌群可能通过参与宿主受体的代谢产物影响肝脏的炎症反应。
更新日期：2018-05-10
中文翻译：
肠道菌群衍生的色氨酸代谢产物可调节肝细胞和巨噬细胞的炎症反应。
肠道菌群在脂肪肝疾病的进展中起着重要作用。然而，调解人及其机制尚待阐明。比较无菌和常规饲养的小鼠与低脂和高脂饮食（HFD）的小鼠之间的代谢物差异，我们鉴定出色胺和3型吲哚乙酸酯（I3A）是取决于微生物群的代谢物，并且在HFD下耗尽。两种代谢物均减少了巨噬细胞中脂肪酸和LPS刺激的促炎性细胞因子的产生，并抑制了细胞向趋化因子的迁移，I3A表现出更大的效价。在肝细胞中，I3A减轻了脂质负荷下的炎症反应，并降低了脂肪酸合酶和固醇调节元件结合蛋白1c的表达。在存在芳基碳氢化合物受体（AhR）拮抗剂的情况下，这些作用被取消，表明该作用是AhR依赖性的。我们的结果表明，肠道菌群可能通过参与宿主受体的代谢产物影响肝脏的炎症反应。
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