Journal
JOURNAL OF LIPID RESEARCH
Volume 61, Issue 1, Pages 70-85Publisher
ELSEVIER
DOI: 10.1194/jlr.RA119000424
Keywords
endocannabinoids; gut microbiome; germ-free phenotype; intestine; fecal microbiota transplant; gene expression; lipidomics
Categories
Funding
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND) - Tri-Agency of the Canadian Federal Government (The Canadian Institutes of Health Research (CIHR)
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Social Sciences and Humanities Research Council of Canada (SSHRC)
- Canadian Foundation of Innovation
- Sentinelle Nord-Apogee program
- Joint International Research Unit for Chemical and Biomolecular Research on the Microbiome and its impact on Metabolic Health and Nutrition (UMI-MicroMeNu) - Sentinelle Nord program
- Fonds Baillet Latour (Grant for Medical Research 2015)
- Fonds de la Recherche Scientifique - FNRS [FNRS FRFS-WELBIO: WELBIO-CR-2019C-02R]
- European Research Council [336452-ENIGMO]
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The gut microbiota is a unique ecosystem of microorganisms interacting with the host through several biochemical mechanisms. The endocannabinoidome (eCBome), a complex signaling system including the endocannabinoid system, approximately 50 receptors and metabolic enzymes, and more than 20 lipid mediators with important physiopathologic functions, modulates gastrointestinal tract function and may mediate host cell-microbe communications there. Germ-free (GF) mice, which lack an intestinal microbiome and so differ drastically from conventionally raised (CR) mice, offer a unique opportunity to explore the eCBome in a microbe-free model and in the presence of a reintroduced functional gut microbiome through fecal microbiota transplant (FMT). We aimed to gain direct evidence for a link between the microbiome and eCBome systems by investigating eCBome alterations in the gut in GF mice before and after FMT. Basal eCBome gene expression and lipid profiles were measured in various segments of the intestine of GF and CR mice at juvenile and adult ages using targeted quantitative PCR transcriptomics and LC-MS/MS lipidomics. GF mice exhibited age-dependent modifications in intestinal eCBome gene expression and lipid mediator levels. FMT from CR donor mice to age-matched GF male mice reversed several of these alterations, particularly in the ileum and jejunum, after only 1 week, demonstrating that the gut microbiome directly impacts the host eCBome and providing a cause-effect relationship between the presence or absence of intestinal microbes and eCBome signaling. These results open the way to new studies investigating the mechanisms through which intestinal microorganisms exploit eCBome signaling to exert some of their physiopathologic functions.
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