Targeting the endocannabinoid system with microbial interventions to improve gut integrity

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 2:106:110169. doi: 10.1016/j.pnpbp.2020.110169. Epub 2020 Nov 11.

Abstract

The endocannabinoid system is a metabolic pathway involved in the communication between the gut microbiota and the host. In the gut, the endocannabinoid system regulates the integrity of the intestinal barrier. A compromised integrity of the intestinal barrier is associated with several disorders such as inflammatory bowel disorder, obesity and major depressive disorder. Decreasing the integrity of the intestinal barrier results in an increased translocation of bacterial metabolites, including lipopolysaccharides, across the epithelial layer of the gut, causing the subsequent inflammation. Targeting the endocannabinoid system in the gut can improve the integrity of the intestinal barrier. Currently, microbial interventions in the form of probiotics are under investigation for the treatment of diseases related to a compromised integrity of the intestinal barrier. However, the role of the endocannabinoid system in the gut is ambiguous since activity of the endocannabinoid system is increased in obesity and decreased in inflammatory bowel disease, emphasizing the need for development of personalized microbial interventions. This review discusses the role of the endocannabinoid system in regulating the gut barrier integrity and highlights current efforts to develop new endocannabinoid-targeted microbial interventions.

Keywords: 2-arachidonoylglycerol; Anandamide; Endocannabinoid system; Gut; Gut brain axis; Intestinal barrier; Microbiota; Probiotic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain-Gut Axis / drug effects
  • Brain-Gut Axis / physiology*
  • Depressive Disorder, Major / diet therapy
  • Depressive Disorder, Major / metabolism*
  • Depressive Disorder, Major / psychology
  • Endocannabinoids / administration & dosage
  • Endocannabinoids / metabolism*
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Probiotics / administration & dosage*

Substances

  • Endocannabinoids