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Ganoderma lucidum polysaccharide modulates gut microbiota and immune cell function to inhibit inflammation and
Cuiling Guo1, Dandan Guo1, Liu Fang1
1College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, PR China.
Abstract:
This study investigated the effects of water-soluble polysaccharide extracted from the sporoderm-removed spores of Ganoderma lucidum (GLP) against AOM/DSS-induced inflammation, tumorigenesis, and gut microbiota modification, which has never been reported before. Our data revealed that GLP (200 and 300 mg/kg) decreased AOM/DSS-induced colitis and tumorigenesis, manifested by significantly reduced disease activity index score, and total number and size of tumors. Furthermore, GLP ameliorated AOM/DSS-induced microbiota dysbiosis, increased short-chain fatty acid production, and alleviated endotoxemia by inhibiting TLR4/MyD88/NF-κB signaling. Besides, GLP profoundly improved gut barrier function as evidenced by increased numbers of goblet cells, MUC2 secretion, and tight junction protein expressions. GLP treatment inhibited macrophage infiltration and downregulated IL-1β, iNOS, and COX-2 expressions. Additionally, GLP inhibited lipopolysaccharides (LPS)-induced inflammation markers and MAPK (JNK and ERK) activation in macrophage RAW264.7, intestinal HT-29, and NCM460 cells. In conclusion, these results indicate that GLP is a promising prebiotic for the treatment of colorectal cancer.
Insights
Ganoderma lucidum polysaccharide (GLP) effectively reduced colorectal cancer development and inflammation in a mouse model. This prebiotic also improved gut barrier function and modulated gut microbiota, showing promise for cancer treatment.
Area of Science:
- Gastroenterology
- Immunology
- Microbiology
Background:
- Colorectal cancer (CRC) poses a significant health burden.
- Inflammation and gut dysbiosis are key factors in CRC development.
- Novel therapeutic strategies targeting the gut microbiome are needed.
Purpose of the Study:
- To investigate the anti-cancer and anti-inflammatory effects of Ganoderma lucidum polysaccharide (GLP).
- To evaluate GLP's impact on AOM/DSS-induced colitis and tumorigenesis.
- To explore GLP's mechanisms of action, including gut microbiota modulation and barrier function improvement.
Main Methods:
- Administration of GLP (200 and 300 mg/kg) to AOM/DSS-induced colitis and tumorigenesis mouse models.
- Assessment of disease activity index, tumor number, and size.
- Analysis of gut microbiota composition, short-chain fatty acid (SCFA) production, and endotoxemia.
- Evaluation of gut barrier function markers (goblet cells, MUC2, tight junctions).
- Inhibition of inflammatory markers (IL-1β, iNOS, COX-2) and signaling pathways (TLR4/MyD88/NF-κB, MAPK) in vitro.
Main Results:
- GLP significantly reduced colitis and tumorigenesis, decreasing disease activity and tumor burden.
- GLP ameliorated gut dysbiosis, increased SCFA production, and alleviated endotoxemia.
- GLP enhanced gut barrier function by increasing goblet cells, MUC2, and tight junction proteins.
- GLP inhibited inflammatory responses in macrophages and intestinal cells by downregulating key signaling pathways.
Conclusions:
- GLP demonstrates significant anti-colitis and anti-tumorigenesis effects.
- GLP acts as a prebiotic, improving gut health and barrier function.
- GLP exerts its effects by modulating gut microbiota and inhibiting inflammatory signaling pathways.
- GLP is a promising prebiotic agent for colorectal cancer prevention and treatment.
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