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Endocannabinoids — at the crossroads between the gut microbiota and host metabolism

Key Points

  • As gut microorganisms interact with host cells via several mechanisms, targeting the microbiota to treat metabolic disorders is an attractive therapeutic approach

  • The endocannabinoid system is involved in numerous biological processes, such as the regulation of energy homeostasis, inflammation and gut-barrier function

  • The endocannabinoid system is altered during the metabolic syndrome, which contributes to the onset of cardiometabolic disease

  • Gut microorganisms and the endocannabinoid system are intertwined

  • The metabolites, receptors and signalling pathways that couple the gut microbiota with the host endocannabinoid system and eventually metabolism require further investigation

  • Although the endocannabinoid system is currently being targeted in several pathological conditions such as obesity, diabetes mellitus and intestinal inflammation, few candidate drugs have been tested in clinical trials

Abstract

Various metabolic disorders are associated with changes in inflammatory tone. Among the latest advances in the metabolism field, the discovery that gut microorganisms have a major role in host metabolism has revealed the possibility of a plethora of associations between gut bacteria and numerous diseases. However, to date, few mechanisms have been clearly established. Accumulating evidence indicates that the endocannabinoid system and related bioactive lipids strongly contribute to several physiological processes and are a characteristic of obesity, type 2 diabetes mellitus and inflammation. In this Review, we briefly define the gut microbiota as well as the endocannabinoid system and associated bioactive lipids. We discuss existing literature regarding interactions between gut microorganisms and the endocannabinoid system, focusing specifically on the triad of adipose tissue, gut bacteria and the endocannabinoid system in the context of obesity and the development of fat mass. We highlight gut-barrier function by discussing the role of specific factors considered to be putative 'gate keepers' or 'gate openers', and their role in the gut microbiota–endocannabinoid system axis. Finally, we briefly discuss data related to the different pharmacological strategies currently used to target the endocannabinoid system, in the context of cardiometabolic disorders and intestinal inflammation.

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Figure 1: Interactions between gut microorganisms, host and metabolism during pathological conditions.
Figure 2: Targeting gut microorganisms and the endocannabinoid system to improve gut-barrier function and host metabolism.

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Acknowledgements

P.D.C. is the recipient of grants from Fonds de la Recherche Scientifique (FNRS) (convention J.0084.15 and convention 3.4579.11), Projet de Recherche (convention: T.0138.14) and Action de Recherche Concertée (Communauté française de Belgique convention 12/17-047). The authors work is also supported by the FNRS for the Fund For Strategic Fundamental Research (FRFS)-WELBIO under grant WELBIO-CR-2012S-02R and in part by the Funds InBev-Baillet Latour (Grant for Medical Research 2015). P.D.C. is also a recipient of a European Research Council Starting Grant 2013 (Starting grant 336452-ENIGMO).

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P.D.C., H.P., M.V.H., L.G., C.D. and A.E. researched data for the article, provided substantial contributions to discussions of the content, and contributed equally to the writing of the article. N.M.D. contributed to discussion of the content. All of the authors reviewed and/or edited the manuscript before its submission.

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Correspondence to Patrice D. Cani.

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Cani, P., Plovier, H., Van Hul, M. et al. Endocannabinoids — at the crossroads between the gut microbiota and host metabolism. Nat Rev Endocrinol 12, 133–143 (2016). https://doi.org/10.1038/nrendo.2015.211

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