Yang P, Wang R, Zhou YP, Wen JF, Yang DX. Berberine alleviates experimental colitis by enhancing gut-microbiota-dependent intestinal barrier function and suppressing gasdermin D activation. World J Gastroenterol 2026; 32(13): 115299 [DOI: 10.3748/wjg.v32.i13.115299]
Corresponding Author of This Article
Dong-Xue Yang, Assistant Professor, Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, The First Affiliated Hospital of Ningbo University, No. 247 Renmin Road, Jiangbei District, Ningbo 315020, Zhejiang Province, China. fyyangdongxue@nbu.edu.cn
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Gastroenterology & Hepatology
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Basic Study
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Apr 7, 2026 (publication date) through Mar 27, 2026
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World Journal of Gastroenterology
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1007-9327
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Yang P, Wang R, Zhou YP, Wen JF, Yang DX. Berberine alleviates experimental colitis by enhancing gut-microbiota-dependent intestinal barrier function and suppressing gasdermin D activation. World J Gastroenterol 2026; 32(13): 115299 [DOI: 10.3748/wjg.v32.i13.115299]
World J Gastroenterol. Apr 7, 2026; 32(13): 115299 Published online Apr 7, 2026. doi: 10.3748/wjg.v32.i13.115299
Berberine alleviates experimental colitis by enhancing gut-microbiota-dependent intestinal barrier function and suppressing gasdermin D activation
Ping Yang, Ran Wang, Yu-Ping Zhou, Jin-Feng Wen, Dong-Xue Yang
Ping Yang, Yu-Ping Zhou, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
Ping Yang, Yu-Ping Zhou, Jin-Feng Wen, Dong-Xue Yang, Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
Ran Wang, Yu-Ping Zhou, Jin-Feng Wen, Dong-Xue Yang, Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
Yu-Ping Zhou, Jin-Feng Wen, Dong-Xue Yang, Institute of Digestive Disease, Ningbo University, Ningbo 315020, Zhejiang Province, China
Co-corresponding authors: Jin-Feng Wen and Dong-Xue Yang.
Author contributions: Yang P contributed to original draft writing and resources; Yang P and Yang DX contributed to methodology and funding acquisition; Wang R and Yang DX contributed to conceptualization; Wang R contributed to visualization and project administration; Zhou YP and Wen JF contributed to formal analysis; Wen JF contributed to validation; Yang DX acquired fundings; Wen JF and Yang DX contributed to review and editing, supervision, and contributed equally as co-corresponding authors; all authors contributed to data curation and approved the final version to publish.
Supported by Zhejiang Provincial Natural Science Foundation of China, No. LQ22H030004 and No. LBY23H200006; Medical Health Science and Technology Project of Zhejiang Provincial Health Commission, No. 2024KY324; Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project, No. 2025ZL115; and Ningbo “Kechuang Yongjiang 2035” Major Research and Development Program, No. 2025Z150; and Ningbo Top Medical and Health Research Program, No. 2023020612.
Institutional animal care and use committee statement: The animal use protocol was approved by the Animal Ethics and Welfare Committee of Ningbo University, No. AEWC-NBU20230299.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: No additional data are available.
Corresponding author: Dong-Xue Yang, Assistant Professor, Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, The First Affiliated Hospital of Ningbo University, No. 247 Renmin Road, Jiangbei District, Ningbo 315020, Zhejiang Province, China. fyyangdongxue@nbu.edu.cn
Received: October 21, 2025 Revised: December 8, 2025 Accepted: January 15, 2026 Published online: April 7, 2026 Processing time: 159 Days and 19.5 Hours
Abstract
BACKGROUND
Ulcerative colitis (UC) is a chronic, recurrent inflammatory disease of the gastrointestinal tract that often presents challenges in clinical management. Traditional Chinese medicine constitutes a significant therapeutic modality for the management of UC. Berberine has demonstrated remarkable therapeutic potential for the treatment of UC.
AIM
To determine whether berberine alleviates dextran sulfate sodium (DSS)-induced UC in mice by enhancing gut microbiota-dependent intestinal barrier function and inhibiting gasdermin D (GSDMD) activation.
METHODS
An acute colitis mouse model was established by administering 3% DSS. The mice were treated daily with berberine (50 mg/kg and 100 mg/kg), after which body weight, colon length, histological scoring, and intestinal levels of inflammatory cytokines were assessed. Intestinal barrier permeability was evaluated, and 16S ribosomal RNA sequencing was conducted. Fecal microbiota transplantation and cohousing studies were performed to determine the role of the gut microbiota. The inhibitory effects of GSDMD were pharmacologically manipulated to substantiate the efficacy and underlying mechanism of action of berberine in treating UC in preclinical models.
RESULTS
Berberine has shown significant potential for alleviating the severity of DSS-induced acute colitis. Fecal microbiota transplantation and cohousing experiments showed that the gut microbiota is indispensable for the beneficial effects of berberine in DSS-induced colitis. Moreover, pharmacological inhibition of GSDMD attenuated the therapeutic efficacy of berberine, highlighting the importance of GSDMD in the mechanism of action.
CONCLUSION
Berberine alleviates experimental colitis by inhibiting the GSDMD-mediated pathway and increasing gut barrier function via a microbiota-mediated approach, thus offering a new molecular target for colitis therapy.
Core Tip: Berberine alleviates dextran sulfate sodium-induced murine ulcerative colitis through a mechanism that involves gut microbiota-dependent enhancement of intestinal barrier function and suppression of gasdermin D activation. Fecal microbiota transplantation and cohousing studies underscore the pivotal role of the microbiota, while gasdermin D inhibition diminishes the therapeutic efficacy of berberine, suggesting a novel therapeutic target for colitis.
