Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1865, Issue 12, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbalip.2020.158786
Keywords
Endocannabinoids; Endocannabinoidome; Microbiota; Microbiome; Gut-brain axis; Fecal microbiota transfer
Funding
- Canada Research Excellence Chair in the MicrobiomeEndocannabinoidome 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
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We investigated the hypothesis that the endocannabinoidome (eCBome), an extension of the endocannabinoid (eCB) signaling system with important functions in the CNS, may play a role in the microbiota-gut-brain axis. Using LC-MS/MS and qPCR arrays we profiled the brain eCBome of juvenile (4 weeks) and adult (13 weeks) male and female germ-free (GF) mice, which are raised in sterile conditions and virtually devoid of microbiota, present neurophysiological deficits, and were found recently to exhibit a strongly altered gut eCBome in comparison to conventionally raised age/sex-matched controls. The causal effect of the gut microbiome on the eCBome was investigated through the re-introduction into adult male GF mice of a functional gut microbiota by fecal microbiota transfer (FMT). The concentrations of the eCB, 2-arachidonoylglycerol (2-AG), and its 2-monoacylglycerol congeners, were significantly reduced in the brain, but not in the hypothalamus, of both juvenile and adult male and adult female GF mice. FMT rendered these decreases non-statistically significant. The eCB, anandamide (AEA), and its congener N-acylethanolamines (NAEs), were instead increased in the brain of adult female GF mice. Saturated fatty acid-containing NAEs were decreased in adult male GF mouse hypothalamus in a manner not reversed by FMT. Only few changes were observed in the expression of eCBome enzymes and receptors. Our data open the possibility that altered eCBome signaling may underlie some of the brain dysfunctions typical of GF mice.
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