Walnut Green Husk Polysaccharide Improve Gut Microbiota and Alleviate Intestinal Inflammation Caused by Immune...

Area of Science:

• Immunology
• Microbiology
• Biochemistry

Background:

• Immune checkpoint inhibitor induced colitis (ICIIC) is a significant side effect of cancer immunotherapy.
• Alterations in intestinal microbiota are linked to the development and severity of ICIIC.
• Therapeutic strategies to manage ICIIC and restore gut homeostasis are urgently needed.

Purpose of the Study:

• To investigate the structure of Walnut green husk polysaccharides (WGHP).
• To evaluate the therapeutic effects of WGHP on ICIIC in a mouse model.
• To explore the impact of WGHP on intestinal microbiota composition and short-chain fatty acid profiles.

Main Methods:

• Structural analysis of WGHP using monosaccharide composition.
• Induction of ICIIC in mice and administration of WGHP.
• Assessment of clinical colitis scores, inflammatory cytokine levels (TNF-α, IL-1β), and gut microbiota analysis (16S rRNA sequencing).
• Measurement of short-chain fatty acids (SCFAs) and analysis of the GPR43/PD-1/PD-L1 signaling pathway.

Main Results:

• WGHP is primarily composed of galacturonic acid, galactose, and arabinose.
• WGHP administration significantly ameliorated ICIIC phenotypes in mice.
• WGHP modulated the Firmicutes/Bacteroides ratio, increased beneficial bacteria like Lactobacillus, and elevated SCFA levels (butyric acid, acetic acid, isobutyric acid).
• WGHP reduced pro-inflammatory cytokines and activated the GPR43/PD-1/PD-L1 pathway, mitigating inflammation.

Conclusions:

• WGHP demonstrates significant therapeutic potential for preventing and treating ICIIC.
• WGHP exerts its beneficial effects by restoring intestinal homeostasis through microbiota modulation and anti-inflammatory mechanisms.
• WGHP can be considered a functional polysaccharide for managing ICIIC.