Rhodotorula mucilaginosa JAASSRY1 Ameliorates Cyclophosphamide-Induced Immunosuppression by Regulating Gut Microbiota and Activation of Spleen TLR4/MyD88/NF-κB Pathway

The present study was designed to evaluate the ameliorative effects of Rhodotorula mucilaginosa JAASSRY1 (JAASSRY1) on cyclophosphamide (CTX)-induced immunosuppression in mice.Immunocompromised mice were established by intraperitoneal injection of CTX (80 mg/kg/bw) for three consecutive days, followed by JAASSRY1 orally administered of JAASSRY1 for 21 days.Various immunological parameters, including immune organ indices, spleen cytokine levels, and immunoglobulin profiles, were evaluated.JAASSRY1 prevented CTX-induced immune damage by reversing weight loss and immune organ atrophy, suppressing the expression of IL-6, IL-17, and IFN-γ in the spleen (P < 0.01), and restoring levels of IgA and IgG, while up-regulating IL-4 (P < 0.01).Furthermore, JAASSRY1 attenuated immunosuppressive spleen injury by modulating the TLR4/MyD88/NF-κB pathway and regulating the Bax/Bcl-2 ratio.JAASSRY1 also alleviated CTX-induced dysbiosis by enhancing the abundance of Colidextribacter and reducing the levels of Parabacteroides and Bacteroides.A significant association was observed between specific gut microbiome Bacteroides and immune parameters (P < 0.01).Above all, JAASSRY1 demonstrates efficacy in ameliorating immunosuppression through the modulation of the "gut microbiotaspleen" axis, providing a basis for the development of probiotic formulations with immunomodulatory properties.