摘要Objective:The probiotic,Bifidobacterium animalis,(B.animalis)is known to provide health benefits in humans.This study investigated the role of B.animalis in suppressing malignant melanoma progression and modulating tumor immunity.Methods:Bifidobacterium spp.were isolated from human faeces and verified by whole-genome sequencing.The anti-tumor effects were assessed in B16-F10 melanoma cells.B.animalis efficacy was further evaluated in a syngeneic murine model.Immune profiling was performed with flow cytometry and CD8+T cell dependency was tested with antibody depletion.Functional metabolites were analyzed by liquid chromatography-mass spectrometry(LC-MS).Transcriptome sequencing elucidated the YAP1 mechanism in CD8+T cells.Gut microbiota composition was assessed via shotgun metagenomic sequencing.Results:Among the selected Bifidobacterium spp.,B.animalis and its conditioned medium effectively inhibited melanoma cell proliferation.Oral administration of B.animalis significantly reduced the growth of B16-F10 allografts,accompanied by an increase in tumor-infiltrating effector T cells.The bioactive component of B.animalis was identified as a<3-kDa non-protein fraction containing mannose,which phenocopied the anti-tumor and immunostimulatory effects of B.animalis.Microbiota profiling revealed probiotic enrichment in mannose-treated mice.CD8+T cell depletion abrogated mannose efficacy.Combination therapy with B.animalis and anti-PD-1 synergistically enhanced tumor control and T cell activation.Mechanistically,the bioactive fraction and mannose downregulated YAP1 expression in CD8+T cells.Conclusions:B.animalis suppresses melanoma tumorigenesis in mice by restoring gut microbiota and secreting functional mannose.Mannose enhances anti-PD-1 efficacy by inhibiting YAP1 expression in CD8+T cells,thereby improving effector function.B.animalis may serve as a preventive measure for melanoma management.