Endocannabinoids and related lipids in host metabolism-gut microbiome signalling

Over the past two decades, it has become clear that the two endocannabinoids, anandamide and 2-arachidonoyl-glycerol, are only the tip of an iceberg of a larger signalling system composed of hundreds of chemically similar fatty acid derivatives, including 2-monoacylglycerols, N-acylethanolamines and other N-acylamines. Unlike the endocannabinoids, these lipids only seldom bind the two cannabinoid receptors, of which CB1 is now recognized as a major player in both the central and peripheral control of energy metabolism. They modulate instead the activity of other G-protein-coupled receptors, as well as of ligand-activated ion channels and nuclear receptors, which also regulate energy intake, accumulation and expenditure. Bacteria inhabiting the gut as part of the intestinal microbiome also produce endocannabinoid-like molecules capable of activating host receptors in vitro. These discoveries led to current research into potential bi-directional communication between this 'extended endocannabinoid system', or endocannabinoidome, and the gut microbiome. Ongoing studies are investigating how this axis might control energy metabolism, particularly in response to diet.