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

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.