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Published on: June 13, 2020
Ginseng polysaccharides ameliorate colorectal tumorigenesis through Lachnospiraceae-mediated immune modulation
Gangfan Zong1, Rui Deng2, Yehua Pan1
1Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Abstract:
Probiotics and their metabolites play a critical role in immunotherapy for colorectal cancer (CRC) and intestinal damage. Identifying specific probiotics from natural products and elucidating the underlying mechanisms represent promising strategies for CRC research. This study investigated the structural characterization and therapeutic potential of ginseng polysaccharides (GPS) in inhibiting tumor growth. The results showed that the molecular weight of GPS was 2425.512 kDa, which was mainly composed of Man, GluA, Gal, Glc, Xyl, and Ara contained in its structure. GPS (100, 200, and 400 mg/kg) significantly ameliorates colorectal tumorigenesis in AOM/DSS-induced and MC38-induced CRC models. 16S rRNA shows that GPS supplementation significantly increased the abundance of Lachnospiraceae compared to the model group. Mechanistically, GPS supplementation promoted the proliferation of beneficial Lachnospiraceae bacterium (L.B.), leading to increased short-chain fatty acids (SCFAs) production. The effective anti-CRC effects of key probiotics were further substantiated by their ability to inhibit myeloid-derived suppressor cells (MDSCs) and enhance the infiltration and activation of CD8+ T cells. These findings highlight the pivotal role of GPS-induced alterations in the potential probiotics L.B. production in CRC suppression, emphasizing the potential of GPS in immune regulation for microbiome-targeted cancer therapies.
Insights
Ginseng polysaccharides (GPS) show promise in fighting colorectal cancer (CRC) by boosting beneficial gut bacteria, leading to increased short-chain fatty acids and enhanced anti-tumor immunity. This natural compound offers a potential microbiome-targeted therapy for CRC.
Area of Science:
- Immunology
- Microbiology
- Natural Products Chemistry
Background:
- Probiotics and their metabolites are crucial in immunotherapy for colorectal cancer (CRC) and intestinal damage.
- Identifying specific probiotics from natural products offers promising strategies for CRC research.
Purpose of the Study:
- To investigate the structural characteristics and therapeutic potential of ginseng polysaccharides (GPS) in inhibiting tumor growth.
- To elucidate the underlying mechanisms of GPS in colorectal cancer suppression.
Main Methods:
- Structural characterization of GPS, including molecular weight and monosaccharide composition (Man, GluA, Gal, Glc, Xyl, Ara).
- Evaluation of GPS therapeutic potential in AOM/DSS-induced and MC38-induced CRC models.
- 16S rRNA sequencing to analyze gut microbiota composition changes.
- Assessment of short-chain fatty acids (SCFAs) production, myeloid-derived suppressor cells (MDSCs), and CD8+ T cell activity.
Main Results:
- GPS (2425.512 kDa) significantly ameliorated colorectal tumorigenesis in CRC models.
- GPS supplementation increased the abundance of Lachnospiraceae, promoting beneficial L.B. proliferation and SCFA production.
- GPS inhibited MDSCs and enhanced CD8+ T cell infiltration and activation, indicating immune regulation.
Conclusions:
- GPS demonstrates significant anti-CRC effects by modulating the gut microbiome and enhancing anti-tumor immunity.
- GPS-induced L.B. production and subsequent SCFA generation play a pivotal role in CRC suppression.
- Ginseng polysaccharides represent a promising natural product for microbiome-targeted cancer therapies and immune regulation in CRC.
