<i>Rhodotorula mucilaginosa</i> 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 (<i>P</i>< 0.01), and restoring levels of IgA and IgG, while up-regulating IL-4 (<i>P</i>< 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 <i>Colidextribacter</i> and reducing the levels of <i>Parabacteroides</i> and <i>Bacteroides</i>. A significant association was observed between specific gut microbiome Bacteroides and immune parameters (<i>P</i>< 0.01). Above all, JAASSRY1 demonstrates efficacy in ameliorating immunosuppression through the modulation of the "gut microbiota-spleen" axis, providing a basis for the development of probiotic formulations with immunomodulatory properties.