Altered endocannabinoid system gene expression in inflammatory bowel disease mucosa: New perspectives in inflammatory bowel disease management

doi:10.4253/wjge.v18.i2.113576

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World Journal of Gastrointestinal Endoscopy

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World J Gastrointest Endosc. Feb 16, 2026; 18(2): 113576
Published online Feb 16, 2026. doi: 10.4253/wjge.v18.i2.113576

Altered endocannabinoid system gene expression in inflammatory bowel disease mucosa: New perspectives in inflammatory bowel disease management

Iulia Andreea Pelisenco, Alessandro Salvi, Giuseppina De Petro, Ioana Andreea Musat, Teodora Ecaterina Manuc, Cristian George Tieranu, Gabriel Becheanu, Elena Milanesi, Maria Dobre

Iulia Andreea Pelisenco, Elena Milanesi, Maria Dobre, Department of Pathology, Victor Babes National Institute of Pathology, Bucharest 050096, Romania

Alessandro Salvi, Giuseppina De Petro, Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia 25123, Lombardy, Italy

Ioana Andreea Musat, Teodora Ecaterina Manuc, Gabriel Becheanu, Elena Milanesi, Maria Dobre, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest 050474, Romania

Teodora Ecaterina Manuc, Gastroenterology and Hepatology, Clinic Fundeni Institute, Bucharest 022328, Romania

Cristian George Tieranu, Gastroenterology, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania

Co-first authors: Iulia Andreea Pelisenco and Alessandro Salvi.

Co-corresponding authors: Teodora Ecaterina Manuc and Elena Milanesi.

Author contributions: Manuc TE and Milanesi E contributed equally and are co-corresponding authors. Pelisenco IA and Salvi A contributed equally to designing the present study, analyzing data, and writing, and are co-first authors; Milanesi E, Dobre M, De Petro G, Musat IA, Manuc TE, Tieranu CG, Becheanu G, contributed to methodology, formal analysis, data extraction, data interpretation, writing, reviewing, and editing; Dobre M contributed to acquisition and supervision. All authors contributed to the interpretation of the study and approved the final version to be published.

Supported by the Romanian Ministry of Research, Innovation, and Digitization, No. PN 23.16.02.04.

Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Fundeni Clinical Institute (No. 8007-23/02/2018), Elias Emergency University Hospital (No. 6598-11/05/2015), and Victor Babes National Institute of Pathology (No. 103-29/07/2022).

Informed consent statement: Informed consent was obtained from all subjects involved in the study.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: All the raw data available from the corresponding author on reasonable request.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Elena Milanesi, Assistant Professor, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Eroii Sanitari Blvd., No. 8, Sector 5, Bucharest 050474, Romania. elena.k.milanesi@gmail.com

Received: August 29, 2025
Revised: September 24, 2025
Accepted: December 4, 2025
Published online: February 16, 2026
Processing time: 159 Days and 15.7 Hours

Abstract

BACKGROUND

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.

AIM

To investigate possible impairment of the genes belonging to ECS by analyzing their expression levels in IBD patients and controls.

METHODS

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.

RESULTS

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).

CONCLUSION

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.

Keywords: Endocannabinoid system; Inflammatory bowel disease; Crohn’s disease; Ulcerative colitis; Gene expression

Core Tip: The anti-inflammatory benefits of cannabinoids could serve as a potential new treatment for patients suffering from inflammatory bowel disease (IBD). In this study, we analyzed the expression level of 10 genes belonging to the endocannabinoid system in colonic mucosa from IBD patients vs controls. CNR2, FAAH, GPR18, GPR55, PPARG, and TRPV1 genes were dysregulated in the entire IBD cohort. Stratifying patients into Crohn's disease and ulcerative colitis subgroups, we found that the same 6 genes were dysregulated in at least one comparison. Further analysis of the endocannabinoid system could bridge the gap between preclinical findings and its role in gastrointestinal diseases.