Format

Send to

Choose Destination
Cell Host Microbe. 2019 May 8;25(5):668-680.e7. doi: 10.1016/j.chom.2019.04.002.

Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis.

Author information

1
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Novartis Institute for Biomedical Research Inc., Cambridge, MA 02139, USA.
3
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
4
Novartis Institute for Biomedical Research Inc., Cambridge, MA 02139, USA.
5
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.
6
W. M. Keck Microscopy Facility, The Whitehead Institute, Cambridge, MA 02142, USA.
7
Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
8
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.
9
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. Electronic address: xavier@molbio.mgh.harvard.edu.

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.

KEYWORDS:

Bacteroides; inflammation; inflammatory bowel disease; innate immunity; metabolism; microbiome; sphingolipids

PMID:
31071294
PMCID:
PMC6544385
[Available on 2020-05-08]
DOI:
10.1016/j.chom.2019.04.002

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center