Funda D, Drabonova B, Golias J, Tejklova T, Cisarova R, Bartosova J, Drastich P. Gluten-free diet reduces severity of dextran sulfate sodium-induced colitis in BALB/c mice. World J Gastroenterol 2026; 32(46): 121572 [DOI: 10.3748/wjg.121572]
Corresponding Author of This Article
David Funda, MD, Senior Scientist, Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Videnska 1083, Prague 140 00, Czech Republic. david.funda@mbu.cas.cz
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
research-article
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World J Gastroenterol. Dec 14, 2026; 32(46): 121572 Published online Dec 14, 2026. doi: 10.3748/wjg.121572
Gluten-free diet reduces severity of dextran sulfate sodium-induced colitis in BALB/c mice
David Funda, Barbora Drabonova, Jaroslav Golias, Tereza Tejklova, Radka Cisarova, Jitka Bartosova, Pavel Drastich
David Funda, Barbora Drabonova, Jaroslav Golias, Tereza Tejklova, Radka Cisarova, Jitka Bartosova, Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague 140 00, Czech Republic
Barbora Drabonova, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences, Prague 165 00, Czech Republic
Pavel Drastich, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
Author contributions: Funda D and Drabonova B designed the research; Golias J, Drabonova B, Tejklova T, Cisarova R and Funda D performed the experiments; Funda D prepared the original manuscript draft; Bartosova J, Drabonova B and Funda D participated in manuscript writing and review; Drabonova B and Bartosova J edited the manuscript and prepared corrections; Funda D and Drastich P supervised the study and acquired funding; all authors have read and approved the final manuscript.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors take full responsibility for the scientific content of the manuscript.
Supported by the AZV Grant from the Ministry of Health of the Czech Republic, No. NU22-06-00269.
Institutional review board statement: This study did not involve human participants or human biological material.
Institutional animal care and use committee statement: Experiments were conducted in compliance with European Directive 2010/63 on the protection of animals used for scientific purposes and were approved by the Institutional Animal Care and Use Committee of the Institute of Microbiology, CAS (approval No. 23-2022-P).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Corresponding author: David Funda, MD, Senior Scientist, Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Videnska 1083, Prague 140 00, Czech Republic. david.funda@mbu.cas.cz
Received: April 13, 2026 Revised: June 5, 2026 Accepted: September 16, 2026 Published online: December 14, 2026 Processing time: 206 Days and 14.8 Hours
Abstract
BACKGROUND
Inflammatory bowel disease is a chronic inflammatory condition in which gut microbiota, intestinal permeability, and nutrition play critical roles. Dietary gluten and its major component gliadin exhibit pro-inflammatory, lipopolysaccharide-like properties that may contribute to intestinal inflammation.
AIM
To investigate whether gluten withdrawal, i.e., a gluten-free diet (GFD), attenuates inflammation in experimental colitis.
METHODS
We investigated the effect of a GFD in dextran sulfate sodium (DSS)-induced colitis using specific-pathogen-free BALB/c mice fed standard or gluten-free Altromin diets for 4 weeks prior to a 1-week exposure to 3% or 2.5% DSS. Both Altromin open-formula diets were comparable in total protein and energy content. Disease severity was assessed by colon length, intestinal bleeding, weight loss, histology, and flow cytometry analysis of colonic leukocytes and selected T-cell subsets in mesenteric lymph nodes and spleen.
RESULTS
Four-week pre-exposure to a GFD led to statistically significant preservation of colon length (P < 0.0001), decreased intestinal bleeding, and improved histology (crypt length and histology score; P < 0.0001). GFD-fed mice displayed a significant reduction in infiltrating colonic lymphocyte antigen 6C+ monocytes (P < 0.0001) and increased proportions of forkhead box P3+ regulatory T cells, interleukin-10+ T helper cells (P < 0.01), and γδ T cells (P < 0.05) in mesenteric lymph nodes, and to a lesser extent in the spleen, indicating an enhanced anti-inflammatory immune profile.
CONCLUSION
Long-term gluten withdrawal substantially reduced DSS-induced colitis in specific-pathogen-free BALB/c mice. These findings suggest that a GFD may represent a safe therapeutic strategy warranting further evaluation in clinical studies.
Core Tip: A gluten-free diet (GFD) markedly attenuated dextran sulfate sodium-induced colitis in BALB/c mice, reducing clinical and histological disease severity. Gluten withdrawal decreased colonic lymphocyte antigen 6C+ monocyte infiltration and promoted anti-inflammatory immune responses, including increased proportions of forkhead box P3+ regulatory T cells and interleukin-10+ T helper cells, as well as γδ T cells. These findings highlight a previously underappreciated role of dietary gluten in intestinal inflammation and support a GFD as a potential non-pharmacological strategy for modulating immune responses in inflammatory bowel disease.
