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United European Gastroenterol J. 2017 Dec;5(8):1108-1115. doi: 10.1177/2050640617698622. Epub 2017 Mar 13.

Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.

Author information

1
Department of Physiology and Pharmacology, La Sapienza University of Rome, Rome, Italy.
2
Department of Clinical Medicine and Surgery, University of Naples 'Federico II', Naples, Italy.
3
Department of Translational Medical Science, University of Naples 'Federico II', Naples, Italy.

Abstract

Background:

Clostridium difficile toxin A is responsible for colonic damage observed in infected patients. Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity.

Objective:

The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A.

Methods:

Caco-2 cells were exposed to Clostridium difficile toxin A (30 ng/ml), with or without cannabidiol (10-7-10-9 M), in the presence of the specific antagonist AM251 (10-7 M). Cytotoxicity assay, transepithelial electrical resistence measurements, immunofluorescence analysis and immunoblot analysis were performed in the different experimental conditions.

Results:

Clostridium difficile toxin A significantly decreased Caco-2 cells' viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251.

Conclusions:

Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.

KEYWORDS:

Clostridium difficile; cannabidiol; cannabinoids; clostridium difficile toxin A; intestinal permeability

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