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

**Authors:** Yunting Deng, Yannan Zhang, Bowen Yan, Jinhai Huo, Weiming Wang

PMC · DOI: 10.3390/cimb48020195 · 2026-02-10

## 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.

## Key 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.

## Linked entities

- **Proteins:** TNF (tumor necrosis factor), IL1B (interleukin 1 beta), FFAR2 (free fatty acid receptor 2), PDCD1 (programmed cell death 1), CD274 (CD274 molecule)
- **Chemicals:** butyric acid (PubChem CID 264), acetic acid (PubChem CID 176), isobutyric acid (PubChem CID 6590)
- **Diseases:** colitis (MONDO:0005292)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Il22 (interleukin 22) [NCBI Gene 50929] {aka IL-22, IL-22a, ILTIFa, If2b1, Iltif}, 16S (DNA segment, 16S) [NCBI Gene 27471], Gpr34 (G protein-coupled receptor 34) [NCBI Gene 23890] {aka Lypsr1}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, Ffar2 (free fatty acid receptor 2) [NCBI Gene 233079] {aka GPCR43, Gpr43}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}
- **Diseases:** Necrosis (MESH:D009336), hyperplasia (MESH:D006965), WGHP (MESH:C564877), hepatocellular carcinoma (MESH:D006528), tissue (MESH:D017695), watery diarrhea (MESH:D003969), inflammatory bowel disease (MESH:D015212), enteritis (MESH:D004751), liver damage (MESH:D056486), ICIIC (MESH:D003092), gastrointestinal reactions (MESH:D005767), lethargy (MESH:D053609), death (MESH:D003643), fever (MESH:D005334), vomiting (MESH:D014839), head and neck squamous cell carcinoma (MESH:D000077195), nausea (MESH:D009325), proctitis (MESH:D011349), intestinal perforation (MESH:D007416), diarrhea (MESH:D003967), cancer (MESH:D009369), dysbiosis (MESH:D064806), asthma (MESH:D001249), abdominal pain (MESH:D015746), Inflammatory (MESH:D007249), injury to (MESH:D014947)
- **Chemicals:** hydrogen (MESH:D006859), apatinib (MESH:C553458), PMP (MESH:C091421), PVDF (MESH:C024865), eosin (MESH:D004801), sulfuric acid (MESH:C033158), SCFAs (MESH:D005232), ribose (MESH:D012266), ether (MESH:D004986), Fuc (MESH:D005643), Glc (MESH:D005947), BA (MESH:D020148), BCA (MESH:C047117), Ara (MESH:D001089), xylose (MESH:D014994), paraformaldehyde (MESH:C003043), lipid (MESH:D008055), ammonium acetate (MESH:C018824), butyrate (MESH:D002087), Rha (MESH:D012210), acetone (MESH:D000096), carbohydrate (MESH:D002241), theobromine (MESH:D013805), MC (MESH:C061001), GalA (MESH:C007819), ochratoxin A (MESH:C025589), TCA (MESH:D014238), H&amp;E (MESH:D006371), Valeric acid (MESH:C038780), Dextran (MESH:D003911), 2-ethylbutyric acid (-), Hematoxylin (MESH:D006416), glucuronic acid (MESH:D020723), SDS (MESH:D012967), AA (MESH:D019342), KBr (MESH:C039004), Gal (MESH:D005690), Isovaleric acid (MESH:C008216), ethanol (MESH:D000431), water (MESH:D014867), phenol (MESH:D019800), Propionic Acid (MESH:C029658), Isobutyric acid (MESH:C020380), lactic acid (MESH:D019344), Polysaccharides (MESH:D011134), xylene (MESH:D014992), sodium pentobarbital (MESH:D010424), polyacrylamide (MESH:C016679), C (MESH:D002244), monosaccharide (MESH:D009005), uronic acid (MESH:D014574), acetonitrile (MESH:C032159), Man (MESH:D008358), CH3OH (MESH:D000432), paraffin (MESH:D010232), O (MESH:D010100), acids (MESH:D000143), sugar (MESH:D000073893)
- **Species:** Eubacterium xylanophilum (species) [taxon 39497], gut metagenome (species) [taxon 749906], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Juglans regia (English walnut, species) [taxon 51240], Lactobacillales (order) [taxon 186826], Lactobacillus johnsonii (species) [taxon 33959], Bacteroides (genus) [taxon 816], Enterorhabdus (genus) [taxon 580024], Homo sapiens (human, species) [taxon 9606], Lactobacillaceae (family) [taxon 33958], Clostridia (class) [taxon 186801], Lycium chinense (Chinese boxthorn, species) [taxon 112883], Mus musculus (house mouse, species) [taxon 10090], Lactobacillus (genus) [taxon 1578], Candidatus Saccharimonas (genus) [taxon 1331051], Anaerotruncus (genus) [taxon 244127]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939954/full.md

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Source: https://tomesphere.com/paper/PMC12939954