The structurally defined polysaccharide of Atractylodes macrocephala Koidz demonstrates the ability to alleviate cyclophosphamide-induced immunosuppression and promote the restoration of intestinal homeostasis in mice.

Atractylodes macrocephala Koidz, is a traditional Chinese herb widely recognized for its dual application in both dietary and medicinal contexts, primarily due to its spleen-strengthening properties. In this study, we isolated a novel water-soluble glycan from this herb, designated as XGM, and aimed to further enhance its potential for development and utilization. To achieve this objective, we elucidated its precise structural characteristics and demonstrated its immunomodulatory effects in a murine model. Structural analysis of XGM, conducted through methylation analysis and nuclear magnetic resonance (NMR) spectroscopy, revealed that it is a homogeneous xyloglucomannan with an average molecular weight of 5.5 kDa. The linear backbone of XGM consisted of α-1,4-D-Glcp and α-1,4,6-D-Glcp residues, with branches comprising terminal β-D-Manp and β-D-Xylp units that were linked to the C-6 position of the α-1,4,6-D-Glcp residues. Oral administration of XGM in mice effectively alleviated cyclophosphamide (CTX)-induced immunosuppression, as indicated by elevated serum levels of TNF-α, IL-10, IgG, and IgM, as well as the normalization of CD4+/CD8+ T cell and Treg cell ratios. Mechanistically, XGM was found to enhance the abundance of beneficial gut microbiota, such as Lactobacillus species, and to restore tryptophan metabolism, a key pathway in intestinal immunity. These findings suggest that XGM exerts its immunomodulatory effects through the regulation of the gut microbiota-metabolite axis, thereby offering novel insights into the spleen-strengthening properties of A. macrocephala and the functional mechanisms of XGM.