GUANGZHOU — Researchers from Southern Medical University in Guangzhou, China, published findings in the May 2026 issue of Cancer Biology & Medicine. The study identified that Bifidobacterium animalis produces mannose, which activates CD8+ T cells and suppresses melanoma progression in mouse models.

The research team isolated five Bifidobacterium species from healthy human stool and screened them for anti-cancer activity. B. animalis was identified as the most potent inhibitor of melanoma cell growth in culture among the species tested.

Oral administration of B. animalis to mice with B16-F10 melanoma tumors reduced tumor volume and weight. B. animalis did not colonize the tumor tissue in the mouse models, indicating its effects were mediated through secreted metabolites. The team identified mannose as the key bioactive molecule, described as a small, non-protein compound under 3 kilodaltons.

Drinking water supplemented with 1% mannose replicated the anti-tumor effects of the live probiotic in mice. Mannose supplementation increased tumor-infiltrating CD8+ T cells and boosted their production of granzyme B, interferon-gamma, and tumor necrosis factor-alpha. Mannose enters CD8+ T cells through the GLUT1 glucose transporter and activates the Hippo signaling pathway.

Activation of the Hippo pathway leads to phosphorylation and cytoplasmic retention of YAP1, a transcription factor that normally suppresses T-cell effector function. Preventing YAP1 from entering the nucleus removes a constraint on T-cell cytotoxicity. When combined with anti-PD-1 therapy, B. animalis produced a synergistic effect, improving tumor control compared to either treatment alone in the mouse models.

"We were surprised to find that a simple sugar like mannose could have such a profound effect on T-cell immunity," the authors said. "What's exciting is that mannose doesn't just activate T cells—it does so by targeting a specific molecular pathway, the Hippo-YAP1 axis, that has not been previously linked to microbial metabolites in cancer immunotherapy." The authors added, "This gives us a clear mechanistic roadmap for how a gut bacterium can systemically influence anti-tumor immunity." They also stated, "The fact that mannose also enriches other beneficial gut bacteria suggests a dual benefit: it directly empowers immune cells while simultaneously fostering a more favorable microbial ecosystem."

More than half of melanoma patients fail to respond to immune checkpoint inhibitors like anti-PD-1 or eventually develop resistance. Melanoma patients often show reduced levels of beneficial gut bacteria, including Bifidobacterium, and lower microbial diversity. The research was supported by the National Natural Science Foundation of China and the Guangzhou Science and Technology Project.