Polygonatum sibiricum is a traditional Chinese medicinal and food homologous substance, usually used after processing with yellow wine. However, its main active ingredient, polysaccharide, has been less studied after wine processing. This study aimed to investigate the effect of Polygonatum polysaccharides after wine processing on the function of immunosuppressed mice and its related mechanisms. The yellow wine processed Polygonatum (YWPP) polysaccharides were extracted by the water extraction alcohol precipitation method. BALB/c mice were used to establish the immunosuppressive animal model with cyclophosphamide (CTX). The immunomodulatory effect of the YWPP polysaccharides Interleukin 2, interferon γ, immunoglobulin A, Immunoglobulin M, T lymphocyte subsets, and other indexes were detected by enzyme-linked immunosorbent assay, flow cytometry, and other technologies. To study the mechanism of immunomodulation of polysaccharides, 16s rDNA sequencing and Gas Chromatography/Mass Spectrometry (GC/MS) were used to analyze the changes of intestinal microbiota composition, diversity, and the content of short-chain fatty acids (SCFAs). The Spearman method was used to analyze the correlation between gut microbiota and various immune indexes and SCFAs. The results showed that the YWPP polysaccharides could significantly restore the body weight of immunosuppressed mice, improve the spleen and thymus, and regulate peripheral blood cell values. The YWPP polysaccharides can also effectively promote Interleukin 2, interferon γ, immunoglobulin A, and immunoglobulin M in immunosuppressed mice and regulate the expression of immune-related indexes. The YWPP polysaccharides promoted the production of SCFAs, significantly regulated the relative abundance of norank_f__norank_o__RF39, Rikenellaceae_RC9_gut_group, norank_f__ UCG-010, and norank_f__norank_o__Clostridia_UCG-014; reversed CTX-induced metabolic abnormalities of mouse gut microbiota; and normalized them. Spearman correlation analysis showed that the relative abundance of gut microbiota was significantly correlated with various immune indices and SCFAs. In conclusion, the YWPP polysaccharides can improve the immune function of CTX-induced immunocompromised mice, promote cytokine upregulation and the relative abundance of immune-related beneficial bacteria in mice, and regulate the gut microbiota, thereby regulating host immunity. The results of this study will provide a theoretical basis for the practical application of the YWPP polysaccharides, health product development, and diversified product development.
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