Tetrahydroxylated bile acids prevents malignant progression of Barret esophagus in vitro by inhibiting the interleukin-1β-nuclear factor kappa-B pathway

doi:10.3748/wjg.v31.i29.107066

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Gastroenterol. Aug 7, 2025; 31(29): 107066
Published online Aug 7, 2025. doi: 10.3748/wjg.v31.i29.107066

Tetrahydroxylated bile acids prevents malignant progression of Barret esophagus in vitro by inhibiting the interleukin-1β-nuclear factor kappa-B pathway

Anatolii Mamchur, Shane Duggan, Hui Xue, Xiao-Jia Niu, Yu-Zhuo Wang, Zhen-Wei Ma, Dermot Kelleher, Victor Ling, Zu-Hua Gao

Anatolii Mamchur, Zhen-Wei Ma, Victor Ling, Zu-Hua Gao, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver V6R2B5, British Columbia, Canada

Shane Duggan, Department of Medicine, Rm 5.408 Life Sciences Institute, University of British Columbia, Vancouver V6T1Z3, British Columbia, Canada

Hui Xue, Xiao-Jia Niu, Department of Experimental Therapeutics, BC Cancer Research Center, Vancouver V5Z0B4, British Columbia, Canada

Yu-Zhuo Wang, Department of Urologic Sciences, Vancouver General Hospital, Vancouver V5Z0B4, British Columbia, Canada

Yu-Zhuo Wang, Department of Experimental Therapeutics, The University of British Columbia, Vancouver V5Z0B4, British Columbia, Canada

Dermot Kelleher, Department of Medicine, University of British Columbia, Vancouver V6T2B5, British Columbia, Canada

Co-first authors: Anatolii Mamchur and Shane Duggan.

Co-corresponding authors: Victor Ling and Zu-Hua Gao.

Author contributions: Mamchur A contributed to design and performance of experiments, data collection and analysis, manuscript writing, interpretation of data; Duggan S contributed to design of experiments, revision and editing of manuscript; Xue H and Niu XJ contributed to revision and editing of manuscript, methodology; Wang YZ and Ma ZW contributed to analysis, interpretation of data, revision and editing of manuscript; Kelleher D contributed to data analysis, revision and editing of manuscript, supervision of the study; Ling V and Gao Z contributed to supervision of the study, design of experiments, manuscript writing, revision and editing of manuscript.

Institutional review board statement: This study does not involve any human experiments. The study has been approved by the institutional biosafety board (No. B22-0164).

Institutional animal care and use committee statement: No animal experiment.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

Data sharing statement: No additional data are available.

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 Non Commercial (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: Zu-Hua Gao, MD, PhD, FRCPC, Professor and Head, Department of Pathology and Laboratory Medicine, University of British Columbia, G105-2211 Wesbrook Mall, Vancouver V6R2B5, British Columbia, Canada. zuhua.gao@ubc.ca

Received: March 18, 2025
Revised: April 29, 2025
Accepted: June 30, 2025
Published online: August 7, 2025
Processing time: 140 Days and 18.5 Hours

Core Tip

Core Tip: Barrett’s esophagus is a pathological precancerous condition. Hydrophobic bile acids could stimulate processes of malignant transition of Barrett esophagus tissue via activation proinflammatory signaling pathways. This study demonstrated that hydrophilic tetrahydroxylated bile acid could inhibit the cytotoxic and proinflammatory action of hydrophobic deoxycholic acid in adult stem cells isolated from Barrett esophagus. Co-treatment with hydrophilic tetrahydroxylated bile acids maintained the metaplastic intestinal-type cells in their differentiated state with preserved histology and mucin production. Thus, tetrahydroxylated bile acids have a potential protective role against the malignant progression of Barrett esophagus.