Unlocking Cannabinoid Secrets in Gut Inflammation

Inflammatory bowel disease (IBD) is a broad classification including various chronic inflammatory gastrointestinal conditions that comprises two main disorders: Crohn's disease (CD) and ulcerative colitis (UC). The key components of the endocannabinoid system (ECS) are highly expressed within the gastrointestinal tract, playing a crucial role in maintaining homeostasis and providing protection against intestinal inflammation. To investigate possible impairment of the genes belonging to ECS by analyzing their expression levels in IBD patients and controls. The paired biopsies of endoscopically inflamed (IM) and noninflamed (NIM) colonic mucosa from 30 IBD-diagnosed patients (17 UC and 13 CD), and the colonic mucosa from 17 non-IBD controls, were collected and analyzed. The messenger RNA expression level of cannabinoid receptor (CNR) 1, CNR 2, diacylglycerol lipase alpha, diacylglycerol lipase beta, fatty acid amide hydrolase (FAAH), G protein-coupled receptor (GPR) 18, GPR55, monoglyceride lipase, peroxisome proliferator-activated receptor gamma (PPARG), and transient receptor potential cation channel, subfamily V, member 1 (TRPV1) was determined by quantitative polymerase chain reaction. Six out of the 10 investigated genes were found to be dysregulated in at least one comparison. Specifically, in IBD patients, FAAH, PPARG, and TRPV1 were significantly downregulated in IM compared to NIM (FAAH, P = 0.012; PPARG, P = 0.001; TRPV1, P = 0.032) and in IM compared to controls (FAAH, P < 0.001; PPARG, P < 0.001; TRPV1, P = 0.002). An opposite trend was reported for CNR2 and GPR55, which showed an upregulation in IM compared to NIM (CNR2, P = 0.005; GPR55, P = 0.001). We found a significant impairment of the ECS in IBD patients. Further analyses on larger cohorts are needed for a better understanding of the potential of cannabinoids in managing IBD.