Yang J, Pan YT, Wen HZ. Growth differentiation factor 15 - a new molecular target in inflammatory bowel disease: Progress and challenges. World J Gastroenterol 2026; 32(5): 115439 [DOI: 10.3748/wjg.v32.i5.115439]
Corresponding Author of This Article
Hong-Zhu Wen, Department of Gastroenterology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, No. 725 Wanping South Road, Xuhui District, Shanghai 200032, China. ellawhz@sina.com
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Gastroenterology & Hepatology
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Editorial
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This article is an open-access article which 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: http://creativecommons.org/licenses/by-nc/4.0/
Feb 7, 2026 (publication date) through Jan 28, 2026
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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
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Yang J, Pan YT, Wen HZ. Growth differentiation factor 15 - a new molecular target in inflammatory bowel disease: Progress and challenges. World J Gastroenterol 2026; 32(5): 115439 [DOI: 10.3748/wjg.v32.i5.115439]
World J Gastroenterol. Feb 7, 2026; 32(5): 115439 Published online Feb 7, 2026. doi: 10.3748/wjg.v32.i5.115439
Growth differentiation factor 15 - a new molecular target in inflammatory bowel disease: Progress and challenges
Jia Yang, Ya-Ting Pan, Hong-Zhu Wen
Jia Yang, Ya-Ting Pan, Department of Oncology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Hong-Zhu Wen, Department of Gastroenterology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Author contributions: Wen HZ designed the editorial and revised the manuscript; Yang J wrote the draft; Pan YT prepared the figure and contributed to the revision of the manuscript; all authors contributed to the important intellectual content of the manuscript.
Supported by National Natural Science Foundation of China, No. 82274285.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Hong-Zhu Wen, Department of Gastroenterology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, No. 725 Wanping South Road, Xuhui District, Shanghai 200032, China. ellawhz@sina.com
Received: October 17, 2025 Revised: November 17, 2025 Accepted: December 15, 2025 Published online: February 7, 2026 Processing time: 104 Days and 2.8 Hours
Abstract
The study by Ruiz-Malagón et al marks a significant advancement in understanding the role of growth differentiation factor 15 (GDF15) in inflammatory bowel disease (IBD). Using both in vivo and in vitro models, the researchers detected elevated circulating GDF15 levels in patients with both ulcerative colitis (UC) and Crohn’s disease (CD), and its level correlates with markers of inflammation and intestinal permeability. Utilizing colonic organoids and T84 cells, they demonstrated that GDF15 increases intestinal permeability by reducing the expression of zonula occludens-1 (ZO-1) and claudin 1. They concluded that targeting GDF15 may offer a promising strategy to preserve intestinal barrier integrity and potentially reducing immune overactivation. However, results from a small-sample sized study (CD patients 21, UC patients 18, and healthy controls 23) signals interpretation with caution. Genetic approaches are needed to validate the findings that GDF15 alters the intestinal barrier and increases permeability by decreasing the levels of ZO-1 and claudin 1. GDF15 serves as a double-edged mediator with context-dependent protective or pathogenic roles, and clarifying this duality is a critical goal for translational research. Overall, the study represents a critical step in understanding the pathogenesis of IBD, highlighting both progresses made and the work still required for clinical translation.
Core Tip: The study by Ruiz-Malagón et al represents an important step toward elucidating the pathogenesis of inflammatory bowel disease, suggesting that growth differentiation factor 15 (GDF15) may contribute to disease development. GDF15 functions as a context-dependent mediator with both protective and pathogenic effects, and clarifying this duality remains a key objective for translational research. Current findings, derived largely from small observational cohorts, should be interpreted with caution and require validation in larger, independent populations. Ultimately, well-designed randomized controlled trials will be essential to establish more definitive evidence.
