Intratumoral delivery of probiotic Ligilactobacillus salivarius H22A013 modulates the melanoma microenvironment and enhances trametinib efficacy

Melanoma, an aggressive and frequently metastatic skin cancer, demands more effective therapies. While probiotics modulate the gut–tumor axis, their indirect action and the use of engineered strains raise concerns over variability and safety. Here, we introduce a direct intratumoral delivery strategy using the native probiotic Ligilactobacillus salivarius H22A013 to remodel the tumor microenvironment (TME). Combined with trametinib, L. salivarius H22A013 elevated IFN-γ and TNF-α levels, enhanced immune cell infiltration, and amplified anti-tumor immunity. Moreover, the strain migrated to the gut, reshaping gut microbiota composition and metabolic output—suppressing spermine/spermidine degradation while promoting valine synthesis, thereby reinforcing systemic tumor suppression. This approach bypasses indirect gut-axis modulation and avoids risks of engineered probiotics, revealing a new paradigm for native probiotics in cancer treatment.