Basic Study
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World J Gastroenterol. May 28, 2024; 30(20): 2709-2725
Published online May 28, 2024. doi: 10.3748/wjg.v30.i20.2709
Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway
Kai-Di Chen, Kui-Ling Wang, Chen Chen, Yi-Jia Zhu, Wen-Wen Tang, Yu-Ji Wang, Ze-Peng Chen, Lin-Hai He, Yu-Gen Chen, Wei Zhang
Kai-Di Chen, Kui-Ling Wang, Chen Chen, Yi-Jia Zhu, Wen-Wen Tang, Yu-Ji Wang, Ze-Peng Chen, Lin-Hai He, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Kai-Di Chen, Kui-Ling Wang, Chen Chen, Yi-Jia Zhu, Wen-Wen Tang, Yu-Ji Wang, Ze-Peng Chen, Lin-Hai He, The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Yu-Gen Chen, Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Yu-Gen Chen, Wei Zhang, Jiangsu Province Key Laboratory of Tumor Systems Biology and Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Yu-Gen Chen, Jiangsu Collaborative Innovation Center of Chinese Medicine in Prevention and Treatment of Tumor, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Co-first authors: Kai-Di Chen and Kui-Ling Wang.
Co-corresponding authors: Yu-Gen Chen and Wei Zhang.
Author contributions: Chen KD, Chen YG and Zhang W conceptualized and designed the research; Chen KD, Wang KL, Chen C, Wang YJ, Chen ZP and He LH performed the experiments; Chen KD, Zhu YJ, Tang WW and Chen YG analyzed the data; Chen KD and Wang KL drafted the manuscript; Zhang W and Chen YG reviewed and edited the manuscript; All authors approved the final manuscript. Chen KD proposed, designed, conducted experiments, performed data analysis and prepared the first draft of the manuscript. Wang KL was responsible for animal care, medication administration, and drafting initial manuscripts. Both authors have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper. Both Zhang W and Chen YG have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors. Zhang W conceptualized, designed, and supervised the whole process of the project. She searched the literature, revised and submitted the early version of the manuscript with the focus on the association between constipation and oxidative stress. Chen YG was instrumental and responsible for data re-analysis and re-interpretation, comprehensive literature search, preparation and submission of the current version of the manuscript with a focus on gut microbiota and serum metabolites as the predictors of constipation and on potential underlying mechanisms. Zhang W and Chen YG applied for and obtained the funds for this research project. This collaboration between Zhang W and Chen YG is crucial for the publication of this manuscript.
Supported by National Natural Science Foundation of China, No. 82374449; China Postdoctoral Science Foundation, No. 2023M731782; Jiangsu Funding Program for Excellent Postdoctoral Talent, No. 2022ZB806; and Jiangsu Province Postgraduate Scientific Research and Innovation Plan, No. KYCX23_2136.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Ethics Committee in Affiliated Hospital of Nanjing University of Traditional Chinese Medicine (Protocol No. 2023DW-006-01).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available. The data presented in this study are available from the corresponding author upon reasonable request at yugen.chen@njucm.edu.cn.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
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: Yu-Gen Chen, MD, PhD, Chief Doctor, Professor, Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Qinhuai District, Nanjing 210029, Jiangsu Province, China. yugen.chen@njucm.edu.cn
Received: January 30, 2024
Revised: April 18, 2024
Accepted: May 7, 2024
Published online: May 28, 2024
Processing time: 118 Days and 2.8 Hours
Core Tip

Core Tip: Constipation is a highly prevalent functional gastrointestinal disorder. Identifying cost-effective and efficient therapeutic modalities for constipation is of paramount importance. In the present study, hydrogen-rich water alleviated constipation by attenuating intestinal oxidative stress through the sirtuin1 (SIRT1)/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway and modulating gut microbiota and serum metabolites. β-leucine and traumatic acid were identified as potential metabolites for the treatment of constipation, inducing increased SIRT1 expression and decreased oxidative stress.