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Simotang Alleviates the Gastrointestinal Side Effects of Chemotherapy by Altering Gut Microbiota

  • Deng, Lijing (Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University) ;
  • Zhou, Xingyi (Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University) ;
  • Lan, Zhifang (Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University) ;
  • Tang, Kairui (Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University) ;
  • Zhu, Xiaoxu (Hubei University of Chinese Medicine) ;
  • Mo, Xiaowei (Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University) ;
  • Zhao, Zongyao (School of Traditional Chinese Medicine, Beijing University of Chinese Medicine) ;
  • Zhao, Zhiqiang (Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University) ;
  • Wu, Mansi (Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University)
  • Received : 2021.10.13
  • Accepted : 2022.02.25
  • Published : 2022.04.28

Abstract

Simotang oral liquid (SMT) is a traditional Chinese medicine (TCM) consisting of four natural plants and is used to alleviate gastrointestinal side effects after chemotherapy and functional dyspepsia (FD). However, the mechanism by which SMT helps cure these gastrointestinal diseases is still unknown. Here, we discovered that SMT could alleviate gastrointestinal side effects after chemotherapy by altering gut microbiota. C57BL/6J mice were treated with cisplatin (DDP) and SMT, and biological samples were collected. Pathological changes in the small intestine were observed, and the intestinal injury score was assessed. The expression levels of the inflammatory factors IL-1β and IL-6 and the adhesive factors Occludin and ZO-1 in mouse blood or small intestine tissue were also detected. Moreover, the gut microbiota was analyzed by high-throughput sequencing of 16S rRNA amplicons. SMT was found to effectively reduce gastrointestinal mucositis after DDP injection, which lowered inflammation and tightened the intestinal epithelial cells. Gut microbiota analysis showed that the abundance of the anti-inflammatory microbiota was downregulated and that the inflammatory microbiota was upregulated in DDP-treated mice. SMT upregulated anti-inflammatory and anticancer microbiota abundance, while the inflammatory microbiota was downregulated. An antibiotic cocktail (ABX) was also used to delete mice gut microbiota to test the importance of gut microbiota, and we found that SMT could not alleviate gastrointestinal mucositis after DDP injection, showing that gut microbiota might be an important mediator of SMT treatment. Our study provides evidence that SMT might moderate gastrointestinal mucositis after chemotherapy by altering gut microbiota.

Keywords

Acknowledgement

This work was supported by grants from Science and Technology Program of Guangzhou, China (202102020834), the Scientific Research Project of Traditional Chinese Medicine Bureau of Guangdong Province, China (20202042), National Natural Science Foundation of China (82173258), Young Teachers Cultivating Project of Sun Yat-sen University (19ykpy54), Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University, Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine (202102010014), and Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization (2021B1212040007).

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