Immunomodulatory Effects of Bifidobacterium bifidum BGN4 in Cyclophosphamide-induced Immunosuppressed Mice via Activation of NK Cells and Macrophages.

The immune system is a highly coordinated network that defends the host against pathogens and maintains physiological homeostasis. Probiotics have emerged as promising immunoregulatory agents; however, the mechanisms by which they modulate innate and adaptive immune responses remain incompletely understood. In this study, we investigated the immunomodulatory potential of Bifidobacterium bifidum BGN4 using in vitro assays and a cyclophosphamide (CP)-induced immunosuppressed mouse model. In vitro, B. bifidum BGN4 treatment markedly enhanced natural killer (NK) cell cytotoxicity against YAC-1 lymphoma target cells and activated macrophages, as evidenced by elevated nitric oxide production, increased secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and upregulated expression of phagocytosis-related genes (Marco, Msr1, and Cd14). These effects were accompanied by activation of MAPK and NF-κB signaling pathways in macrophages. In vivo, oral administration of B. bifidum BGN4 significantly mitigated CP-induced reductions in body weight, spleen and thymus indices, and leukocyte counts. Moreover, B. bifidum BGN4 enhanced splenocyte proliferation under both basal and mitogen-stimulated conditions and improved NK cell cytotoxic activity in immunosuppressed mice. Collectively, these findings demonstrate that B. bifidum BGN4 promotes both innate and adaptive immune activation, effectively counteracting CP-induced immunosuppression. This probiotic strain represents a promising functional food ingredient for immune enhancement and recovery.