Mineral crude drug mirabilite (Mangxiao) inhibits the occurrence of colorectal cancer by regulating the Lactobacillus–bile acid–intestinal farnesoid X receptor axis based on multiomics integration analysis

Xiaohang Zhou, Hui Sun, Junling Ren, Guangli Yan, Le Yang, Honglian Zhang, Haitao Lu, Xinghua Li, Toshiaki Makino*, Fengting Yin, Jing Li, Xijun Wang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

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Abstract

Mineral crude drug has revolutionized the treatment landscape in precision oncology niche that leads to the improvement in therapeutic efficiency on various tumor subtypes. Mangxiao (MX), a mineral crude drug in traditional Chinese medicine, has been used for treating gastrointestinal diseases for thousands of years. However, the action mechanisms are still ambiguous. Here, we attempt to explore inhibitory roles and associated pharmacological mechanisms of MX upon colorectal cancer (CRC) in APCMin/+ male mice by integrating metabolomics, 16S rDNA sequencing analyses, and metagenomic-based microbiota analysis. We found that MX can significantly inhibit the occurrence of CRC through the regulation of the dysregulated gut microbe metabolism. Furthermore, the correlation analysis of metabolomes and 16S rDNA revealed that MX could restore the disorders of gut microbes by specifically enriching the abundance of Lactobacilli to improve bile acid metabolism, which further activated the farnesoid X receptor (FXR) in CRC mice, then the improvement of gut dysbiosis could inhibit the development of CRC. Collectively, our effort confirmed MX has the capacity to intervene the development of CRC and further discovered that it targets Lactobacillus–bile acid–intestinal FXR axis, which can be regarded as a candidate medicine for future drug discovery and development against CRC.
Original languageEnglish
Article numbere556
Pages (from-to)e556
Number of pages18
JournalMedComm
Volume5
Issue number5
Early online date25 Apr 2024
DOIs
Publication statusPublished - May 2024

Scopus Subject Areas

  • Drug Discovery
  • Genetics(clinical)
  • Biochemistry, medical
  • Genetics
  • Oncology
  • Immunology and Allergy
  • Computer Science Applications
  • Cell Biology

User-Defined Keywords

  • colorectal cancer
  • Mangxiao
  • multiomics
  • traditional Chinese medicine

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