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

TL;DR

This study shows that walnut green husk polysaccharides can improve gut health and reduce intestinal inflammation caused by immune checkpoint inhibitors in mice.

Contribution

The study introduces walnut green husk polysaccharides as a novel functional polysaccharide for preventing immune checkpoint inhibitor-induced colitis.

Findings

WGHP regulates gut microbiota composition and increases short-chain fatty acids in mice with ICIIC.

WGHP reduces pro-inflammatory cytokines TNF-α and IL-1β to alleviate intestinal inflammation.

WGHP activates the GPR43/PD-1/PD-L1 signaling pathway to restore intestinal homeostasis.

Abstract

In this study, the structure of Walnut green husk polysaccharides (WGHP) and their effects on immune checkpoint inhibitor induced colitis (ICIIC) and intestinal microbiota in mice were studied. The results showed that WGHP was composed of mannose (Man) 0.56%, rhamnose (Rha) 6.81%, galacturonic acid (GalA) 53.52%, glucose (Glc) 8.93%, galactose (Gal) 13.94%, arabinose (Ara) 15.88% and fucose (Fuc) 0.35%. The results of animal experiments showed that the intake of WGHP could not only effectively improve the phenotype of ICIIC in mice, but also significantly regulate the composition of intestinal flora and the content of short-chain fatty acids in mice, such as regulating the ratio of Firmicutes/Bacterotoides, Lachnospiraceae NK4A136 group, Lactobacillus, and increasing the content of butyric acid, acetic acid, and isobutyric acid to restore intestinal homeostasis. In addition, WGHP improves inflammation in mouse ICIIC by inhibiting the secretion of pro-inflammatory cytokines TNF-α and IL-1β, thereby activating the GPR43/PD-1/PD-L1 signaling pathway. Therefore, WGHP can be used as a functional polysaccharide for the prevention of ICIIC.

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