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
Affiliations
Xiaohang Zhou
State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine National Chinmedomics Research Center National TCM Key Laboratory of Serum Pharmacochemistry Metabolomics Laboratory Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine Harbin China
Hui Sun
State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine National Chinmedomics Research Center National TCM Key Laboratory of Serum Pharmacochemistry Metabolomics Laboratory Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine Harbin China
Junling Ren
State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine National Chinmedomics Research Center National TCM Key Laboratory of Serum Pharmacochemistry Metabolomics Laboratory Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine Harbin China
Guangli Yan
State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine National Chinmedomics Research Center National TCM Key Laboratory of Serum Pharmacochemistry Metabolomics Laboratory Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine Harbin China
Le Yang
State Key Laboratory of Dampness Syndrome The Second Affiliated Hospital Guangzhou University of Chinese Medicine Guangzhou China
Honglian Zhang
Department of Traditional Chinese Medicine, Pharmacy CollegeQiqihar Medical UniversityQiqihar China
Haitao Lu
Hong Kong Traditional Chinese Medicine Phenome Research Centre, School of Chinese MedicineHong Kong Baptist UniversityHong Kong China
Xinghua Li
State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine National Chinmedomics Research Center National TCM Key Laboratory of Serum Pharmacochemistry Metabolomics Laboratory Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine Harbin China
Toshiaki Makino
Department of Pharmacognosy Graduate School of Pharmaceutical Sciences Nagoya City University Nagoya Japan
Fengting Yin
State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine National Chinmedomics Research Center National TCM Key Laboratory of Serum Pharmacochemistry Metabolomics Laboratory Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine Harbin China
Jing Li
State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine National Chinmedomics Research Center National TCM Key Laboratory of Serum Pharmacochemistry Metabolomics Laboratory Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine Harbin China
Xijun Wang
State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine National Chinmedomics Research Center National TCM Key Laboratory of Serum Pharmacochemistry Metabolomics Laboratory Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine Harbin China
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.
