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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Systems Microbiology
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1481111

Gut microbiota mediates the pro-pyroptosis effect of Xierezhuyubuxu decoction in hepatocellular carcinoma

Provisionally accepted
Zhili Zeng Zhili Zeng 1*Xiushen Li Xiushen Li 2Fan He Fan He 3Enxin Zhang Enxin Zhang 4Zebiao Cao Zebiao Cao 5
  • 1 The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
  • 2 Shenzhen University General Hospital, Shenzhen, China
  • 3 The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, China
  • 4 Shenzhen Baoan Pure Traditional Chinese Medicine Treatment Hospital, Shenzhen, China
  • 5 Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Xierezhuyubuxu decoction (XRZYBXD) is prepared by adding and reducing the Dahuang Zhechong Pill, which is a traditional Chinese medicinal formula in “The Synopsis of Prescriptions of the Golden Chamber”. XRZYBXD has previously been reported to have good efficacy in treating Hepatocellular carcinoma (HCC) in clinical and basic research. However, its underlying mechanism in treating HCC has not been fully elucidated. The aim of the study is to investigate the pro-pyroptosis effect of XRZYBXD in HCC and the role of gut microbiota in this process. Firstly, we executed comprehensive analyses of XRZYBXD on pyroptosis, intestinal flora, microbial metabolites and intestinal barrier function using TUNEL, IHC, ELISA, WB, Q-PCR, 16S rRNA sequencing, and untargeted metabolomics in a H22 tumor-bearing mice model. Further, through rescue experiment of antibiotics-induced microbiota depletion and fecal microbial transplantation (FMT) experiment, the mechanism of XRZYBXD promoting pyroptosis of HCC by improving intestinal flora was verified. We found that XRZYBXD medium and high dose significantly inhibited the growth of tumor and induced pyroptosis of hepatoma cells. They also modified intestinal ecological disorders by expansion of the abundance of beneficial bacteria (such as Akkermansia muciniphila and Parabacteroides distasonis) and reduction of the abundance of harmful bacteria (such as Barnesiella intestinihominis). Accordingly, microbiota metabolites and intestinal barrier function were also significantly improved by XRZYBXD. Further, elimination of gut microbiota by antibiotics weakened the efficacy of XRZYBXD, and FMT with feces from the XRZYBXD high dose group achieved similar therapeutic efficacy as XRZYBXD. In brief, XRZYBXD promote pyroptosis of hepatoma cells via adjusting intestinal dysbiosis.

    Keywords: Xierezhuyubuxu decoction, Hepatocellular Carcinoma, pyroptosis, intestinal flora, FMT, fecal microbial transplantation

    Received: 15 Aug 2024; Accepted: 24 Dec 2024.

    Copyright: © 2024 Zeng, Li, He, Zhang and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zhili Zeng, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China

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