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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Wumei Pills enhance intestinal stem cell - mediated repair in chemotherapy-induced mucositis via Lactobacillus reuteri - dependent modulation of the gut microbiota
Dong-Xue Lu, Zi-Xuan Wang, Xi-Min Liu, Hua Wu, Li-Jiang Ji, Jing Yan
Dong-Xue Lu, Hua Wu, Department of Nutrition, Acupuncture and Moxibustion and Massage College & Health Preservation and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Zi-Xuan Wang, Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008, Jiangsu Province, China
Xi-Min Liu, Department of Prevention and Treatment of Disease, Changzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Changzhou 213003, Jiangsu Province, China
Li-Jiang Ji, Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu 215500, Jiangsu Province, China
Jing Yan, Key Laboratory for Metabolic Diseases in Chinese Medicine, The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Co-first authors: Dong-Xue Lu and Zi-Xuan Wang.
Co-corresponding authors: Li-Jiang Ji and Jing Yan.
Author contributions: Lu DX and Wang ZX designed the study; Liu XM and Wu H collected and analyzed the data; Ji LJ and Yan J processed the data and created the figures and are co-corresponding authors; Lu DX wrote the manuscript; Lu DX and Wang ZX contributed equally to this manuscript and are co-first authors. Yan J will be designated as the one person who takes primary responsibility for communication with the journal during the manuscript submission, peer review, and publication processes. All authors read and approved the final manuscript.
Supported by the Natural Science Research Project of Higher Education Institutions in Jiangsu Province, No. 23KJB360013; China and Jiangsu Province Traditional Chinese Medicine Science and Technology Development Program, No. MS2023001; and Guiding Project of Changshu Science and Technology Development Plan, No. CSWS202411.
Institutional animal care and use committee statement: The study was approved by the Institutional Animal Care and Use Committee of the Nanjing University of Chinese Medicine (Approval No. 202409A097).
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: There is no data 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 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: Jing Yan, PhD, Adjunct Associate Professor, Key Laboratory for Metabolic Diseases in Chinese Medicine, The First Clinical Medical College, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, Jiangsu Province, China.
yanjing@njucm.edu.cn
Received: March 17, 2025
Revised: May 10, 2025
Accepted: August 25, 2025
Published online: September 26, 2025
Processing time: 195 Days and 1.8 Hours
BACKGROUND
Intestinal mucositis is a severe and common complication of chemotherapy, characterized by disruption of the gut microbiota, intestinal inflammation, and epithelial barrier damage. Intestinal stem cells (ISCs) are essential for epithelial renewal and barrier maintenance, yet chemotherapy impairs ISC proliferation and function, delaying mucosal repair. We hypothesized that Wumei Pills (WMP) could protect against chemotherapy-induced intestinal mucositis by modulating gut microbiota - particularly Lactobacillus reuteri (L. reuteri) - to restore ISC activity, preserve microbial balance, reduce inflammation, and promote epithelial regeneration.
AIM
To characterize these changes and the safety of WMP via a 5-fluorouracil (5-FU) induced intestinal mucositis mouse model.
METHODS
In this study, we established a 5-FU induced intestinal mucositis mouse model, to explore the protective effect of WMP regulating L. reuteri on integrity of intestinal mucosa.
RESULTS
We found that intestinal flora is an important mechanism causing chemotherapy-induced intestinal mucositis, but WMP and live L. reuteri were effective in protecting the morphology of intestinal mucositis and normal proliferation of epithelial. L. reuteri colonized in the intestinal mucosa and WMP ameliorated intestinal mucosa damage caused by 5-FU treatment, including improvement of body weight, pathological change, and proliferation level, reducement proinflammatory cytokine secretion (tumor necrosis factor-α, interleukin-6) and the lipopolysaccharides concentration in serum. The repair process stimulated by both L. reuteri and WMP were also accompanied with increased leucine-rich-repeat-containing G-protein-coupled receptor 5 (+) and proliferating cell nuclear antigen of mice intestine. Furthermore, we demonstrated that WMP and L. reuteri activated the Wingless-type/β-catenin pathway to accelerate proliferation of intestinal epithelial, thus recovering damaged intestinal mucosa. However, the relieving effect of L. reuteri on intestinal mucosa was inferior to that of WMP.
CONCLUSION
Our findings indicate that WMP regulating L. reuteri protects intestinal barrier and activates intestinal epithelial proliferation, which sheds light on treatment approaches for intestinal inflammation based on ISCs with traditional Chinese medicine and probiotics L. reuteri.
Core Tip: In this study, we established a 5-fluorouracil induced intestinal mucositis mouse model, and found that intestinal flora is an important mechanism causing chemotherapy-induced intestinal mucositis. Lactobacillus reuteri colonized in the intestinal mucosa and Wumei Pills ameliorated intestinal mucosa damage caused by 5-fluorouracil treatment, including improvement of body weight, pathological change, and proliferation level, reducement proinflammatory cytokine secretion (tumor necrosis factor-α, interleukin-6) and the lipopolysaccharides concentration. The repair process stimulated were also accompanied with increased leucine-rich-repeat-containing G-protein-coupled receptor 5 (+) and proliferating cell nuclear antigen. Furthermore, Wumei Pills and Lactobacillus reuteri activated the Wingless-type/β-catenin pathway to accelerate proliferation of intestinal epithelial, thus recovering damaged intestinal mucosa.
