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World J Gastroenterol. Jul 28, 2026; 32(28): 118458
Published online Jul 28, 2026. doi: 10.3748/wjg.118458
Published online Jul 28, 2026. doi: 10.3748/wjg.118458
Impairment of the intestinal epithelium barrier through alteration of proliferation and differentiation balance in alcohol use disorder
Ami G Toulehohoun, Bouchra Illiyas, Luca Maccioni, Joaquim Lupianez, Rita Manco, Laure-Alix Clerbaux, Peter Stärkel, Laboratory of Gastroenterology (GAEN), Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels 1200, Belgium
Jérôme Ambroise, Centre de Technologies Moléculaires Appliquées Platform, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels 1200, Belgium
Caroline Bouzin, IREC Imaging Platform Belgium (2IP, RRID: SCR_023378), Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels 1200, Belgium
Bernd Schnabl, Department of Medicine, University of California San Diego, La Jolla and VA San Diego Healthcare System, California City, CA 92093-0063, United States
Peter Stärkel, Department of Hepato-Gastroenterology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels 1200, Belgium
Co-corresponding authors: Ami G Toulehohoun and Peter Stärkel.
Author contributions: Toulehohoun AG and Stärkel P carried out the conceptualization as co-corresponding authors; Toulehohoun AG and Ambroise J performed data curation and executed software analysis; Toulehohoun AG, Ambroise J, and Stärkel P performed the formal analysis; Toulehohoun AG and Maccioni L implemented the methodology; Stärkel P supervised the manuscript; Toulehohoun AG, Illiyas B, Maccioni L, and Lopianez J carried out research validation; Toulehohoun AG, Stärkel P, Bouzin C, and Manco R performed visualization; Toulehohoun AG wrote the original draft; Stärkel P, Bouzin C, Manco R, Ambroise J, Maccioni L, Clerbaux LA, and Schnabl B undertook writing, reviewing and editing. All authors approved the final version to publish.
Supported by Fond National de Recherche Scientifique Belgium, No. T.0217.18, No. J.0195.24, and No. T.0195.22; and Action de Recherche Concertée, Université Catholique de Louvain, Belgium by National Institutes of Health, No. 5R01AA024726-08, No. 5R01AA020703-05, No. 5U01AA026939-05, No. 1R01AA031710-01A1, and No. 5P30DK120515-07.
Institutional review board statement: This study protocol was approved by the Institution’s Human Research and Ethical Committee (Comité Ethique Hospitalo-facultaire, Cliniques Universitaires Saint Luc), No. B403201422657. Written informed consent was obtained from all patients and controls. Patients hospitalized for selective alcohol withdrawal in a dedicated alcohol withdrawal unit and controls undergoing out-patient upper gastro-intestinal endoscopy for dyspepsia or reflux symptoms were recruited. Control patients were only retained for the study if they had a normal gastro-intestinal endoscopy and no histological changes on the biopsy samples.
Conflict-of-interest statement: Schnabl B has been consulting for Ambys Medicines, Ferring Research Institute, Gelesis, HOST Therabiomics, Intercept Pharmaceuticals, Mabwell Therapeutics, Patara Pharmaceuticals, Surrozen, and Takeda; Schnabl B’s institution UC San Diego has received research support from Axial Biotherapeutics, BiomX, ChromoLogic, CymaBay Therapeutics, Intercept Pharmaceuticals, NGM Biopharmaceuticals, Prodigy Biotech, and Synlogic Operating Company. Schnabl B is founder of Nterica Bio.
Data sharing statement: sharing statement: The raw data that support the findings of this study are available from the corresponding authors upon request. Raw 16S sequencing reads are available in the National Center for Biotechnology Information Sequence Read Archive under BioProject accession PRJNA705611 and BioSample IDs SAMN18094194-SAMN18094231.
Corresponding author: Ami G Toulehohoun, Laboratory of Gastroenterology (GAEN), Institut de Recherche Expérimentale et Clinique, UCLouvain, Avenue Mounier 52, Brussels 1200, Belgium. ami.toulehohoun@uclouvain.be
Received: January 4, 2026
Revised: February 17, 2026
Accepted: April 7, 2026
Published online: July 28, 2026
Processing time: 188 Days and 11.8 Hours
Revised: February 17, 2026
Accepted: April 7, 2026
Published online: July 28, 2026
Processing time: 188 Days and 11.8 Hours
Core Tip
Core Tip: The effects of alcohol on the human intestinal epithelium are poorly understood, as existing studies are limited, inconsistent, and largely based on animal models that incompletely reflect human pathology. Human-based analyses reveal that heavy alcohol consumption disrupts intestinal epithelial homeostasis by altering stem cell niche and lineage commitment. Duodenal crypts displayed increased depth and expanded proliferation driven by enlarged OLFM4+ stem-like compartments and elevated Ki67+ and CD44+ cells. Ethanol induced aberrant proliferation, impaired secretory lineage commitment, antimicrobial defense and nutrient transport. Using human intestinal organoids, we confirm a direct, Wnt-independent proliferative effect of ethanol on epithelial cells.