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ResearchIn-Press PreviewClinical ResearchGastroenterologyImmunology Open Access | 10.1172/jci.insight.207319

Duodenal macrophages depletion and dysfunction contribute to gut barrier dysfunction in alcohol use disorder

Yifan Hu,1 Jerome Ambroise,2 Luca Maccioni,1 Laure-Alix Clerbaux,1 Caroline Bouzin,3 Bernd Schnabl,4 and Peter Stärkel1

1Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

2Centre de Technologies moléculaires appliquées, Université catholique de Louvain, Brussels, Belgium

3IREC Imaging Platform, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

4Department of Medicine, University of California San Diego, La Jolla, United States of America

Find articles by Hu, Y. in: PubMed | Google Scholar

1Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

2Centre de Technologies moléculaires appliquées, Université catholique de Louvain, Brussels, Belgium

3IREC Imaging Platform, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

4Department of Medicine, University of California San Diego, La Jolla, United States of America

Find articles by Ambroise, J. in: PubMed | Google Scholar

1Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

2Centre de Technologies moléculaires appliquées, Université catholique de Louvain, Brussels, Belgium

3IREC Imaging Platform, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

4Department of Medicine, University of California San Diego, La Jolla, United States of America

Find articles by Maccioni, L. in: PubMed | Google Scholar

1Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

2Centre de Technologies moléculaires appliquées, Université catholique de Louvain, Brussels, Belgium

3IREC Imaging Platform, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

4Department of Medicine, University of California San Diego, La Jolla, United States of America

Find articles by Clerbaux, L. in: PubMed | Google Scholar

1Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

2Centre de Technologies moléculaires appliquées, Université catholique de Louvain, Brussels, Belgium

3IREC Imaging Platform, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

4Department of Medicine, University of California San Diego, La Jolla, United States of America

Find articles by Bouzin, C. in: PubMed | Google Scholar |

1Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

2Centre de Technologies moléculaires appliquées, Université catholique de Louvain, Brussels, Belgium

3IREC Imaging Platform, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

4Department of Medicine, University of California San Diego, La Jolla, United States of America

Find articles by Schnabl, B. in: PubMed | Google Scholar

1Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

2Centre de Technologies moléculaires appliquées, Université catholique de Louvain, Brussels, Belgium

3IREC Imaging Platform, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

4Department of Medicine, University of California San Diego, La Jolla, United States of America

Find articles by Stärkel, P. in: PubMed | Google Scholar

Published November 3, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.207319.
Copyright © 2026, Hu et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 3, 2026 - Version history
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Abstract

In alcohol use disorder (AUD), duodenal macrophage number are reduced, but the underlying mechanisms and consequences for gut permeability remain unknown. Actively drinking AUD patients undergoing standardized inpatient detoxification and healthy controls were enrolled. Fasting blood samples and duodenal biopsies were analyzed using proteomics, histology, multiplex immunohistofluorescence, flow cytometry, and quantitative polymerase chain reaction. Circulating monocytes were differentiated ex vivo into macrophages to assess migration, differentiation, phagocytosis, and cytokine release following stimulation with bacterial products. Gut permeability was evaluated using urinary 51Chromium- ethylenediaminetetraacetic acid excretion, and plasma surrogate markers of microbial translocation. AUD patients showed markedly reduced duodenal macrophages despite increased circulating monocytes and tissue monocyte-attracting chemokines. AUD monocytes exhibited reduced CCR2 expression and downregulation of tissue proteins involved in adhesion and trans-endothelial migration, thereby decreasing mucosal infiltration. Early macrophage differentiation associated was impaired, with reduced CSF1, CSF2, IL-34, and CSF1 receptor expression. Despite preserved phagocytic capacity, residual tissue macrophages displayed a mixed immune phenotype with reduced expression of scavenger receptors involved in microbial responses and cytokine hyporesponsiveness to lipopolysaccharide and peptidoglycan. Reduced macrophage numbers correlated with increased intestinal permeability and markers of microbial translocation. These results link disruption of the duodenal monocyte-macrophage axis to intestinal barrier failure in AUD.

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