Immuno-stimulatory activity of Astragalus polysaccharides in cyclophosphamide-induced immunosuppressed mice by regulating gut microbiota

Evidence has indicated the immune-stimulatory effect of Astragalus polysaccharides (APS), yet it remains unknown whether the potential mechanism is associated with gut microbiota. In this study, we aimed to investigate the role of gut microbiota in APS-initiated immune-enhancing activity in mice. BALB/c mice were injected with cyclophosphamide to establish a mouse immunosuppression model. We found that APS significantly ameliorated the immunosuppression in mice, indicative of the increased immune organ indices, the promoted proliferation of immune cells, and the up-regulated intestinal inflammation. Western blot analysis demonstrated that APS treatment significantly activated Toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK) pathways in the intestine. By 16S rDNA sequencing, APS treatment reversed the gut microbiota dysbiosis in immunocompromised mice. At the genus level, APS increased the abundance of bacteria (like Lactobacillus, Bifidobacteria, Roseburia, and Desulfovibrio) and decreased the content of several bacteria (like Oscillibacter, Tyzzerella, and Lachnoclostridium). However, APS had no immune-enhancing effect on immunocompromised mice with gut microbiota depletion. In conclusion, APS can enhance immune responses in immunocompromised mice by modulating gut microbiota dysbiosis.