A study published in eGastroenterology investigated the role of cannabinoid receptor 1 (CBR1) in intestinal permeability, commonly called “leaky gut.” In particular, the study focused on CBR1’s mechanism in alcohol binge-induced leaky gut to determine how inhibiting CBR1 function can protect the intestinal barrier.
Scientists from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) at the National Institutes of Health (NIH) found that binge drinking increases endocannabinoid levels in the proximal small intestine. This condition activates the CBR1 in intestinal epithelial cells and consequently disrupts tight junction proteins that support gut lining health. Increased intestinal permeability risks increased entry of harmful bacteria and toxins into the bloodstream, which can cause inflammation and other health complications. The study highlighted how CB1R activation in the gut epithelium triggers key factors exacerbating leaky gut when it influences the ERK1/2 signaling pathway’s regulation of tight junction proteins and decreases villus length.
To investigate the CB1R mechanism, the research team used genetically modified mice with intestinal epithelial-specific CB1R deletion. The researchers introduced a peripherally restricted CB1R antagonist (S)-MRI-1891 to observe the effects of pharmacological CB1R inhibition. This compound successfully prevented increased intestinal permeability when administered to normal mice before alcohol intake. The researchers found that alcohol binge drinking significantly increased gut permeability in normal mice, but they did not observe this effect in mice that underwent intestinal epithelial-specific CB1R deletion. This finding suggests that CB1R is a key mediator of alcohol-induced leaky gut.
The findings offer critical insights that can enhance alcohol-related digestive disorder treatment. Targeting CB1R with peripherally restricted antagonists could potentially minimize systemic inflammation and other debilitating gut barrier symptoms associated with excessive drinking.
These insights could have broader applications in gastrointestinal health beyond alcohol-related gut disorders. The endocannabinoid system is known to influence gut motility, immune function, and microbiota composition, and its role in intestinal permeability suggests that CB1R inhibition may be beneficial in other conditions characterized by increased gut permeability, such as inflammatory bowel disease and metabolic disorders.
Future research will explore how combining CB1R inhibitors with other therapeutic strategies could reduce alcohol-induced organ damage, as well as the safety and efficacy of CB1R antagonists in clinical treatments.
Sources: eGastroenterology, Eureka News Alert