Dong WW, Liu T, He LX, He WT. Targeting pyroptosis in inflammatory bowel disease: A potentially effective therapeutic approach. World J Gastroenterol 2025; 31(43): 111358 [DOI: 10.3748/wjg.v31.i43.111358]
Corresponding Author of This Article
Wen-Ting He, PhD, Doctor, The Second Hospital and Clinical Medical School, Lanzhou University, No. 82 Cuiyingmen, Chengguan District, Lanzhou 730030, Gansu Province, China. hewt@lzu.edu.cn
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Gastroenterology & Hepatology
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Minireviews
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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/
Nov 21, 2025 (publication date) through Nov 20, 2025
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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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Dong WW, Liu T, He LX, He WT. Targeting pyroptosis in inflammatory bowel disease: A potentially effective therapeutic approach. World J Gastroenterol 2025; 31(43): 111358 [DOI: 10.3748/wjg.v31.i43.111358]
World J Gastroenterol. Nov 21, 2025; 31(43): 111358 Published online Nov 21, 2025. doi: 10.3748/wjg.v31.i43.111358
Targeting pyroptosis in inflammatory bowel disease: A potentially effective therapeutic approach
Wei-Wei Dong, Tao Liu, Li-Xia He, Wen-Ting He
Wei-Wei Dong, Tao Liu, Wen-Ting He, The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou 730030, Gansu Province, China
Wei-Wei Dong, Tao Liu, Wen-Ting He, Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
Wei-Wei Dong, Tao Liu, Wen-Ting He, Digestive System Tumor Prevention and Treatment and Translational Medicine Engineering Innovation Center of Lanzhou University, Lanzhou University, Lanzhou 730000, Gansu Province, China
Li-Xia He, Division of Molecular and Cellular Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, United States
Co-corresponding authors: Li-Xia He and Wen-Ting He.
Author contributions: He WT and He LX conceived the topic; Dong WW wrote the original manuscript; He WT, He LX and Liu T revised the review; all authors have read and agreed to the published version of the manuscript.
Supported by the Science and Technology Program of Gansu Province, No. 23JRRA1015.
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: Wen-Ting He, PhD, Doctor, The Second Hospital and Clinical Medical School, Lanzhou University, No. 82 Cuiyingmen, Chengguan District, Lanzhou 730030, Gansu Province, China. hewt@lzu.edu.cn
Received: June 30, 2025 Revised: September 14, 2025 Accepted: October 21, 2025 Published online: November 21, 2025 Processing time: 144 Days and 22.9 Hours
Abstract
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic intestinal inflammation with complex pathogenesis. Pyroptosis a pro-inflammatory programmed cell death mediated by gasdermin D (GSDMD) cleavage plays a pivotal role in disease progression through nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)/caspase-1 classical and caspase-4/5/11 non-classical pathways. Targeting pyroptosis has emerged as a promising therapeutic strategy, with recent advances highlighting the potential of pyroptosis inhibitors such as small-molecule compounds, biologics, and repurposed drugs that specifically target NLRP3, caspases, or GSDMD to suppress inflammasome activation, block pore formation, and mitigate downstream inflammation. This review systematically summarizes the mechanisms and therapeutic effects of these inhibitors, while addressing critical challenges including drug specificity, delivery efficiency, and long-term safety, and explores their potential in combination therapies with existing IBD treatments to enhance clinical efficacy. By integrating preclinical and clinical evidence, we provide valuable insights into the translational prospects of pyroptosis-targeted therapies for precision management of IBD.
Core Tip: This review examines pyroptosis as a pivotal mechanism in inflammatory bowel disease (IBD) pathogenesis, driving inflammation and tissue damage. It evaluates therapeutic strategies targeting pyroptosis pathways, emphasizing their potential to modulate disease progression. Key challenges including drug specificity, delivery, and safety are analyzed, alongside opportunities for combination therapies. The discussion highlights the need for precision approaches and improved translational models to advance pyroptosis-targeted treatments for IBD. Future directions focus on overcoming current limitations to optimize clinical outcomes.
