Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis
Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis
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DOI：
10.1016/j.chom.2019.04.002
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发表时间：
2019-05-08
影响因子：
30.3
通讯作者：
Xavier, Ramnik J.
中科院分区：
文献类型：
--
作者：
Brown, Eric M.;Ke, Xiaobo;Xavier, Ramnik J.
鞘脂是真核生物细胞膜的结构成分和重要的信号分子。鞘脂调节炎症和免疫，是炎症性肠病（IBD）患者粪便中含量最高的代谢物。拟杆菌门的共生细菌也产生鞘脂，但这些代谢产物对宿主途径的影响在很大程度上是未知的。为了确定细菌鞘脂是否调节肠道健康，我们用鞘脂缺陷的多形拟杆菌菌株定殖无菌小鼠。缺乏类杆菌衍生的鞘脂导致小鼠的肠道炎症和宿主神经酰胺池改变。使用脂质组学分析，我们描述了鞘脂的生物合成途径，并揭示了各种类杆菌衍生的鞘脂，包括神经酰胺磷酸肌醇和脱氧鞘脂。在IBD代谢组学数据集中注释拟杆菌鞘脂揭示了IBD中较低的丰度以及与炎症和宿主鞘脂产生的负相关性。这些数据突出了细菌鞘脂在维持肠道内稳态和共生中的作用。
Sphingolipids are structural membrane components and important eukaryotic signaling molecules. Sphingolipids regulate inflammation andimmunity and were recently identified as the most differentially abundant metabolite in stool from inflammatory bowel disease (IBD) patients. Commensal bacteria from the Bacteroidetes phylum also produce sphingolipids, but the impact of these metabolites on host pathways is largely uncharacterized. To determine whether bacterial sphingolipids modulate intestinal health, we colonized germ-free mice with a sphingolipid-deficient Bacteroides thetaiotaomicron strain. A lack of Bacteroides-derived sphingolipids resulted in intestinal inflammation and altered host ceramide pools in mice. Using lipidomic analysis, we described a sphingolipid biosynthesis pathway and revealed a variety of Bacteroides-derived sphingolipids including ceramide phosphoinositol and deoxy-sphingolipids. Annotating Bacteroides sphingolipids in an IBD metabolomic dataset revealed lower abundances in IBD and negative correlations with inflammation and host sphingolipid production. These data highlight the role of bacterial sphingolipids in maintaining homeostasis and symbiosis in the gut.