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Multi-dimensional immunoprotection of Ganoderma lucidum spore oil in immunosuppressed mice via microbiome-proteome-metabolome network analysis
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  • Published: 02 March 2026

Multi-dimensional immunoprotection of Ganoderma lucidum spore oil in immunosuppressed mice via microbiome-proteome-metabolome network analysis

  • Shuqi Deng1 na1,
  • Xiaoxiao Wu2,3 na1,
  • Wendong Xu4,
  • Xu Wu3,
  • Hongfei Cai4,
  • Shengpeng Wang5,
  • Juyan Liu4 &
  • …
  • Jiliang Cao1 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biochemistry
  • Immunology
  • Microbiology

Abstract

Ganoderma lucidum has a long-standing history of use as a medicinal mushroom, with its spore oil (GLSO) extracted from broken cell walls using CO2 supercritical extraction. However, there is a notable scarcity of experimental studies on the protective effects and underlying mechanisms of GLSO on immune function impairment. The present study aims to explore the characteristics that GLSO contributes to protecting immune functions in cyclophosphamide-induced immunocompromised mice through a multi-omics analysis approach. GLSO administration significantly improved serum hemolysin levels, macrophage phagocytosis, and NK cell activity in immunosuppressed mice. Metagenomics, metabolomic, and proteomic analyses revealed that the immune protection mediated by GLSO was associated with structural rearrangements within gut microflora and shifts in microbial diversity. Specifically, there was an increase in beneficial microorganisms and a decrease in pathogenic organisms, accompanied by various alterations in metabolites and protein expressions. The identified 5 metabolites (propionic acid, beta-glycyrrhetinic acid, 3-aminosalicylic acid, creatine, and 2-phenylacetamide) and 5 proteins (Slc9a9, Blm, Hk3, AP1M2, and J chain) might serve as potential mediators of GLSO to alleviate immune dysfunction collectively caused by CYP in immunosuppressed mice.

Data availability

The Proteome datasets generated and/or analysed during the current study are available in the PRIDE repository (ProteomeXchange accession: PXD067907; Project Webpage: https://www.ebi.ac.uk/pride/archive/projects/PXD067907). The raw sequence data of Metagenome reported in this paper have been deposited in the Genome Sequence Archive (Genomics, Proteomics & Bioinformatics 2025) in National Genomics Data Center (Nucleic Acids Res 2025)114,115, China National Center for Bioinformation / Beijing Institute of Genomics, Chinese Academy of Sciences (GSA: CRA038543) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa/browse/CRA038543. The data of Metabolome reported in this paper have been deposited in the OMIX, China National Center for Bioinformation / Beijing Institute of Genomics, Chinese Academy of Sciences (https://ngdc.cncb.ac.cn/omix: accession no.OMIX014930).

Abbreviations

AGC:

An automatic gain control

ANOVA:

One-way analysis of variance

BW:

Body weigh

Ctrl:

Control

CYP:

Cyclophosphamide

CYP + L:

Cyclophosphamide + low-dose Ganoderma lucidum spore oil

CYP + H:

Cyclophosphamide + high-dose Ganoderma lucidum spore oil

GLSO:

Ganoderma lucidum spore oil

GPCRs:

G protein-coupled receptors

HC50 :

Half hemolysis value

HCD:

Higher energy collisional dissociation

HPLC:

High Performance Liquid Chromatography

NETs:

Neutrophil extracellular traps

NK:

Natural killer

NMDS:

Non-metric multidimensional scaling

OD:

Optical density

OTUs:

Operational Taxonomic Units

PERMANOVA:

Permutational multivariate analysis of variance

PLS-DA:

Partial least squares discriminant analysis

SCFAs:

Short-chain fatty acids

SRBC:

Sheep red blood cells

TMT:

Tandem Mass Tag

UHPLC-MS/MS:

Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry

YAC-1 cells:

Mouse lymphoma cell line

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Funding

This work was financially supported by Shenzhen Science and Technology Project (JCYJ20220530153201003), Natural Science Foundation of Top Talent of SZTU (GDRC202119), National Natural Science Foundation of China (82104362), Research Founding of Post-doctor who came to Shenzhen (20211063010055), Shandong Province Traditional Chinese Medicine Industry Project (SDAIT-20-05) and Guangdong Province Key Discipline Construction Research Project (2022ZDJS119).

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Author notes

  1. Shuqi Deng and Xiaoxiao Wu contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, Shenzhen Technology University, Shenzhen, China

    Shuqi Deng & Jiliang Cao

  2. Department of GCP Center, Ya’an People’s Hospital, Ya’an, China

    Xiaoxiao Wu

  3. Cell Therapy & Cell Drugs Key Laboratory of Luzhou, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China

    Xiaoxiao Wu & Xu Wu

  4. National Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug Innovation, Guangzhou HanFang Pharmaceutical Co., Ltd, Guangzhou, China

    Wendong Xu, Hongfei Cai & Juyan Liu

  5. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China

    Shengpeng Wang

Authors
  1. Shuqi Deng
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  2. Xiaoxiao Wu
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Contributions

Shuqi Deng: Conceptualization, Investigation, and Data curation, Writing-original draft. Xiaoxiao Wu: Investigation, Data curation, and Writing-original draft. Wendong Xu: Investigation and Data curation. Xu Wu: Writing-review & editing. Hongfei Cai: Data curation. Shengpeng Wang: Writing-review & editing. Juyan Liu: Data curation and Writing-review & editing. Jiliang Cao: Conceptualization, Project administration, Funding, acquisition, and Writing-review & editing. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Juyan Liu or Jiliang Cao.

Ethics declarations

Compliance with ethics requirements

All animal experiments were approved by the Committee on Use and Care of Animals of Southwest Medical University (Reference number 20190810-008; approved on 10 August 2019), and conducted in accordance with the committee’ s guidelines and relevant regulations, particularly RRIVE guidelines.

Competing interests

The authors declare no competing interests.

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Cite this article

Deng, S., Wu, X., Xu, W. et al. Multi-dimensional immunoprotection of Ganoderma lucidum spore oil in immunosuppressed mice via microbiome-proteome-metabolome network analysis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40137-x

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  • Received: 05 November 2025

  • Accepted: 10 February 2026

  • Published: 02 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-40137-x

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Keywords

  • Ganoderma lucidum spore oil
  • Immunity
  • Immunosuppression
  • Gut microbiota
  • Metabolomics
  • Proteomics
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