Structural basis of immunomodulation by edible fungal polysaccharides: From molecular characteristics to action...

Edible Fungal polysaccharides as Immunomodulators: A Systematic Review at the Crossroads of Immunology, Natural Products Chemistry, and Microbiology. The chemical structure-specifically molecular weight, branching degree, and functional group modifications-directly dictates immunological activity. For instance, high-molecular-weight β-glucans activate macrophage surface receptors through triple-helix conformations, whereas sulfation enhances electrostatic interactions with immune cells. Mechanistically, polysaccharides regulate macrophage polarization, dendritic cell maturation, and T/B cell activation, therebyengaging core signaling pathways such as TLR4/MyD88/NF-κB, NLRP3 inflammasome, and MAPK, This orchestrates synergistic enhancement of innate and adaptive immunity. Recent research further demonstrate that polysaccharides can also reshape the gut microbiota-immune metabolic axis by promoting the production of short-chain fatty acids (SCFAs) and activating receptors (e.g., GPR43), indirectly modulating systemic immune responses. Clinically, polysaccharides from Ganoderma lucidum and Lentinus edodes demonstrate efficacy in cancer adjuvant therapy by enhancing immune function and reducing radiotherapy/chemotherapy side effects. However, species-specific receptor recognition heterogeneity and lack of standardized preparation protocols impede clinical translation. Therefore,the implementing an integrated strategy of "polysaccharide structure-immunometabolic reprogramming-precision delivery" to overcome the existing bottlenecks. Combining multi-omics approaches (e.g., gut metagenomics and metabolomics) will advance therapeutics targeting microbiota-immune crosstalk. Such strategies aim to address chronic inflammatory inflammation", malignancies, and related pathologies with enhanced mechanistic specificity.