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Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis.
Brown, Eric M; Ke, Xiaobo; Hitchcock, Daniel; Jeanfavre, Sarah; Avila-Pacheco, Julian; Nakata, Toru; Arthur, Timothy D; Fornelos, Nadine; Heim, Cortney; Franzosa, Eric A; Watson, Nicki; Huttenhower, Curtis; Haiser, Henry J; Dillow, Glen; Graham, Daniel B; Finlay, B Brett; Kostic, Aleksandar D; Porter, Jeffrey A; Vlamakis, Hera; Clish, Clary B; Xavier, Ramnik J.
Afiliación
  • Brown EM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Ke X; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Novartis Institute for Biomedical Research Inc., Cambridge, MA 02139, USA.
  • Hitchcock D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Jeanfavre S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Avila-Pacheco J; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Nakata T; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Arthur TD; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Fornelos N; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Heim C; Novartis Institute for Biomedical Research Inc., Cambridge, MA 02139, USA.
  • Franzosa EA; 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.
  • Watson N; W. M. Keck Microscopy Facility, The Whitehead Institute, Cambridge, MA 02142, USA.
  • Huttenhower C; 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.
  • Haiser HJ; Novartis Institute for Biomedical Research Inc., Cambridge, MA 02139, USA.
  • Dillow G; Novartis Institute for Biomedical Research Inc., Cambridge, MA 02139, USA.
  • Graham DB; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Finlay BB; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
  • Kostic AD; 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.
  • Porter JA; Novartis Institute for Biomedical Research Inc., Cambridge, MA 02139, USA.
  • Vlamakis H; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Clish CB; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Xavier RJ; 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
Cell Host Microbe ; 25(5): 668-680.e7, 2019 05 08.
Article en En | MEDLINE | ID: mdl-31071294
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingolípidos / Simbiosis / Bacteroides thetaiotaomicron / Interacciones Microbiota-Huesped / Intestinos Límite: Animals Idioma: En Revista: Cell Host Microbe Asunto de la revista: MICROBIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingolípidos / Simbiosis / Bacteroides thetaiotaomicron / Interacciones Microbiota-Huesped / Intestinos Límite: Animals Idioma: En Revista: Cell Host Microbe Asunto de la revista: MICROBIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos