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Wuda granules target estrogen receptors and modulate gut microbiota to alleviate postoperative ileus: A multi-omics perspective
Tao Wang, Yi-Hua Xu, Yang-Hui Ou, Wen-Jun Xiong, Li-Jie Luo, Jin Li, Yao-Hui Peng, Yan Chen, Hai-Ping Zeng, Yang Yu, Hai-Peng Tang, Fei Wang, Hong-Liang Yao, Wei Wang
Tao Wang, Wen-Jun Xiong, Li-Jie Luo, Jin Li, Yao-Hui Peng, Yan Chen, Hai-Ping Zeng, Yang Yu, Hai-Peng Tang, Wei Wang, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
Tao Wang, Wen-Jun Xiong, Li-Jie Luo, Jin Li, Yao-Hui Peng, Yan Chen, Hai-Ping Zeng, Yang Yu, Hai-Peng Tang, Wei Wang, Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
Yi-Hua Xu, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou 510315, Guangdong Province, China
Yang-Hui Ou, Hong-Liang Yao, Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou 510260, Guangdong Province, China
Fei Wang, Changshan Hospital of Traditional Chinese Medicine, Quzhou 324200, Zhejiang Province, China
Co-corresponding authors: Hong-Liang Yao and Wei Wang.
Author contributions: Wang T, Yao HL, and Wang W drafted the manuscript; Wang T, Tang HP, and Wang F performed the visualization; Wang T, Ou YH, Xiong WJ, Luo LJ, Tang HP, and Wang W conducted the methodology; Wang T, Xu YH, Ou YH, Li J, Zeng HP, and Wang W performed the investigation; Li J, Xu YH, and Wang W contributed to the formal analysis; Peng YH and Chen Y performed the validation; Yu Y conducted the data curation; Yao HL and Wang W contributed to the conceptualization and supervision equally as co-corresponding authors; Wang W performed the manuscript review and editing; all authors have read and approved the final version of the manuscript.
Supported by National Natural Science Foundation of China, No. 82205109 and No. 82304895; Youth Science and Technology Talent Cultivation Program 2025-2026 of Guangdong Association for Science and Technology, No. SKXRC2025212; Guangzhou Science and Technology Bureau Basic and Applied Basic Research Project, No. 2025A04J3690; Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine, No. 20261103; Young and Middle-aged Backbone Cultivation Project of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 09005650055; Supporting Scientific Research Fund of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 09005647001; and Guangzhou Basic and Applied Basic Research Foundation, No. 2023A04J0461.
Institutional animal care and use committee statement: The study was reviewed and approved by the Institutional Ethical Committee for Animal Research of Institute of Zoology, Guangdong Academy of Science, No. GIZ20240408-02.
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: Data supporting the findings of this study are available from the corresponding author upon request.
Corresponding author: Wei Wang, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Courtyard 16, Jichang Road, Guang
zhou 510405, Guangdong Province, China.
wangwei16400@163.com
Received: October 31, 2025
Revised: December 13, 2025
Accepted: February 6, 2026
Published online: April 21, 2026
Processing time: 166 Days and 22 Hours
BACKGROUND
Postoperative ileus (POI) is a common postsurgical complication characterized by impaired gastrointestinal (GI) motility and inflammation. Wuda granules (WDG), derived from the classical simo decoction, have been clinically used to enhance intestinal motility, normalize bowel activity, relieve obstruction-related discomfort, and promote stool and gas elimination.
AIM
To investigate the therapeutic effects and underlying mechanisms of WDG in alleviating POI.
METHODS
A POI mice model was established by standardized intestinal manipulation. GI motility was assessed by measuring gastric emptying, intestinal transit, and serum levels of GI hormones. Histopathological injury, inflammatory cytokines, and intestinal barrier markers were evaluated. A multi-omics strategy was applied, including proteomics to identify WDG-regulated signaling pathways, 16S rRNA sequencing to characterize microbiota alterations, gas chromatography-tandem mass spectrometry to quantify gut microbial short-chain fatty acids, and molecular docking to predict interactions between WDG-derived compounds and estrogen receptors (ERs).
RESULTS
WDG significantly improved GI motility, restored the serum levels of cholecystokinin, gastrin and motilin, and ameliorated the pathological damage in the colon and small intestine. WDG suppressed intestinal inflammation and preserved epithelial barrier integrity by enhancing the expression of tight-junction proteins and reducing D-lactate levels. Proteomics analysis revealed that WDG modulated estrogen signaling-related proteins and pathways. WDG also rebalanced the gut microbiota, particularly enriching beneficial species such as Bacteroides acidifaciens and Parabacteroides goldsteinii, and increased the production of isovaleric acids. Furthermore, WDG upregulated the expression of tyrosine-protein kinase kit, anoctamin-1, neuronal nitric oxide synthase, and ER expression.
CONCLUSION
WDG alleviates POI by enhancing GI motility, normalizing hormones levels, suppressing inflammation, repairing barrier integrity, and modulating ERs, gut microbiota, and short-chain fatty acids, thereby highlighting a mechanistically relevant inflammation-estrogen-microbiota axis.
Core Tip: Postoperative ileus (POI) is a frequent postsurgical complication. This study shows that Wuda granules (WDG), derived from the classical formula simo decoction, alleviate POI through coordinated actions on inflammation, epithelial barrier repair, intestinal pacemaker function, and gut microbiota remodeling. Multi-omics analysis revealed that WDG activates estrogen receptor signaling and enriches beneficial bacterial species linked to isovaleric acid production. These findings identify an inflammation-estrogen-microbiota axis as a key mechanism, supporting the therapeutic potential of WDG for POI management.
