Role of Gut Microbiota in Cannabinoid-Mediated Suppression of Inflammation

Abstract

Cannabinoids and the endocannabinoid system have been well established to play a crucial role in the regulation of the immune response. Also, emerging data from numerous investigations unravel the imperative role of gut microbiota and their metabolites in the maintenance of immune homeostasis and gut barrier integrity. In this review, we concisely report the immunosuppressive mechanisms triggered by cannabinoids, and how they are closely associated with the alterations in the gut microbiome and metabolome following exposure to endogenous or exogenous cannabinoids. We discuss how cannabinoid-mediated induction of microbial secondary bile acids, short chain fatty acids, and indole metabolites, produced in the gut, can suppress inflammation even in distal organs. While clearly, more clinical studies are necessary to establish the cross talk between exo- or endocannabinoid system with the gut microbiome and the immune system, the current evidence opens a new avenue of cannabinoid-gut-microbiota-based therapeutics to regulate immunological disorders.

Keywords: cannabinoids; drug abuse; endocannabinoids; inflammation; microbiota.

FIGURE 1

Cannabinoids and gut microbiota. (A) Cannabinoid mediated microbiome modulation: endogenous or exogenous cannabinoids increase the beneficial bacteria which produce TJPs that improve gut barrier integrity and AMPs that eliminate pathogens. (B) Immunomodulatory mechanisms of microbial metabolites: microbiota generated secondary bile acids, SCFAs, and indole metabolites modulate various receptors leading to decreased pro-inflammatory cytokines and immune suppression. AhR, aryl hydrocarbon receptor; AMP, antimicrobial protein; CBR, cannabinoid receptor; CBs, cannabinoids; CNS, central nervous system; eCBs, endocannabinoids; FXR, farnesoid X receptor; GPR, G-protein-coupled receptors; HDACs, histone deacetylases; IFN, interferon; IL, interleukin; K, potassium; TJP, tight junction proteins; T-reg, regulatory T cell.