Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis.,Cell Host & Microbe

当前位置： X-MOL 学术 › Cell Host Microbe › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis.
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2019-05-08 , DOI: 10.1016/j.chom.2019.04.002
Eric M Brown ₁ , Xiaobo Ke ₂ , Daniel Hitchcock ₃ , Sarah Jeanfavre ₃ , Julian Avila-Pacheco ₃ , Toru Nakata ₃ , Timothy D Arthur ₃ , Nadine Fornelos ₃ , Cortney Heim ₄ , Eric A Franzosa ₅ , Nicki Watson ₆ , Curtis Huttenhower ₅ , Henry J Haiser ₄ , Glen Dillow ₄ , Daniel B Graham ₃ , B Brett Finlay ₇ , Aleksandar D Kostic ₈ , Jeffrey A Porter ₄ , Hera Vlamakis ₁ , Clary B Clish ₃ , Ramnik J Xavier ₉

Affiliation

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Novartis Institute for Biomedical Research Inc., Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Novartis Institute for Biomedical Research Inc., Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
W. M. Keck Microscopy Facility, The Whitehead Institute, Cambridge, MA 02142, USA.
Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; Department of Microbiology and Immunology, Harvard Medical School, Boston, MA 02115, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Sphingolipids are structural membrane components and important eukaryotic signaling molecules. Sphingolipids regulate inflammation and immunity 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.

中文翻译：

拟杆菌属的鞘脂对维持肠道稳态和共生至关重要。

鞘脂是膜的结构成分和重要的真核信号分子。鞘脂调节炎症和免疫力，最近被确定为炎症性肠病（IBD）患者粪便中差异最大的代谢产物。来自门生拟杆菌的共生细菌也产生鞘脂，但是这些代谢物对宿主途径的影响在很大程度上没有表现出来。为了确定细菌鞘脂是否能调节肠道健康，我们用鞘脂缺乏的拟杆菌（theactotaidesmicron）菌株定植了无细菌的小鼠。缺乏拟杆菌属的鞘脂会导致小鼠肠道炎症并改变宿主神经酰胺库。使用脂质组分析，我们描述了鞘脂的生物合成途径，并揭示了多种由拟杆菌属衍生的鞘脂，包括神经酰胺磷酸肌醇和脱氧鞘脂。注释IBD代谢组学数据集中的拟南芥鞘脂脂表明，IBD的丰度较低，并且与炎症和宿主鞘脂产生负相关。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。

更新日期：2019-05-08

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南