Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels
Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels
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DOI：
10.1038/s41467-020-16274-w
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发表时间：
2020-05-18
影响因子：
16.6
通讯作者：
Ley, Ruth E.
中科院分区：
文献类型：
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作者：
Johnson, Elizabeth L.;Heaver, Stacey L.;Ley, Ruth E.
肠道微生物与宿主代谢有关，但具体机制仍有待发现。神经酰胺是一种鞘脂（SL），与胰岛素抵抗（IR）至肝脂肪变性等一系列代谢紊乱的发生有关。SL从饮食中获得，并在哺乳动物组织中通过从头合成产生。哺乳动物SL的另一个潜在但未探索的来源是由拟杆菌属（Bacteroidetes）产生的，拟杆菌属是肠道微生物组的优势门。拟杆菌属的基因组其近亲编码丝氨酸棕榈酰转移酶（SPT），使其能够产生SL。在这里，我们探讨SL生产肠道拟杆菌宿主SL稳态的贡献。在人类细胞培养中，细菌SL通过宿主SL代谢途径加工。在小鼠模型中，类杆菌衍生的脂质转移到宿主上皮组织和肝门静脉。施用B。对小鼠，而不是SPT缺陷型菌株，多形核昔酸减少了从头SL产生并增加了肝神经酰胺。这些结果表明，肠道来源的细菌SL影响宿主的脂质代谢。神经酰胺是一种鞘脂（SL），已被证明在几种代谢紊乱中发挥作用。在这里，作者研究了肠道拟杆菌产生SL对宿主SL稳态的影响，并表明微生物组来源的SL进入宿主循环并改变神经酰胺的产生。
Gut microbes are linked to host metabolism, but specific mechanisms remain to be uncovered. Ceramides, a type of sphingolipid (SL), have been implicated in the development of a range of metabolic disorders from insulin resistance (IR) to hepatic steatosis. SLs are obtained from the diet and generated by de novo synthesis in mammalian tissues. Another potential, but unexplored, source of mammalian SLs is production by Bacteroidetes, the dominant phylum of the gut microbiome. Genomes of Bacteroides spp. and their relatives encode serine palmitoyltransfease (SPT), allowing them to produce SLs. Here, we explore the contribution of SL-production by gut Bacteroides to host SL homeostasis. In human cell culture, bacterial SLs are processed by host SL-metabolic pathways. In mouse models, Bacteroides-derived lipids transfer to host epithelial tissue and the hepatic portal vein. Administration of B. thetaiotaomicron to mice, but not an SPT-deficient strain, reduces de novo SL production and increases liver ceramides. These results indicate that gut-derived bacterial SLs affect host lipid metabolism. Ceramides are a type of sphingolipid (SL) that have been shown to play a role in several metabolic disorders. Here, the authors investigate the effect of SL-production by gut Bacteroides on host SL homeostasis and show that microbiome-derived SLs enter host circulation and alter ceramide production.