Toward Microbiome-Informed Melanoma Care: The Gut Microbiota in Melanoma Evolution, Immunotherapy Response and...

The gut microbiome (GM) has emerged as a pivotal modulator of melanoma pathogenesis and progression through its influence on systemic inflammation, immune surveillance, and antitumor immunity. Inter-individual variability in GM composition may underlie differences in immune checkpoint inhibitor (ICI) responsiveness and the development of immune-related adverse events (irAEs). This review aims to synthesize current knowledge on the complex interplay between the GM, host immunity, and melanoma, emphasizing its relevance to disease development, therapeutic response, and toxicity.

Both preclinical and clinical evidence have demonstrated that alterations in microbial diversity and composition can affect melanoma outcomes. Depletion or imbalance of specific microbial taxa has been linked to an increased risk of melanoma development or, conversely, to reduced tumor burden. In patients treated with ICIs, distinct taxonomic GM signatures have been correlated with therapeutic efficacy and the likelihood of developing irAEs. Emerging studies have also explored strategies to modulate the GM-including diet, antibiotics, probiotics, and fecal microbiota transplantation-to restore gut "eubiosis" and enhance antitumor immune responses. The intricate crosstalk between the gut microbiome, host immunity, and melanoma significantly influences disease biology and treatment outcomes. A deeper understanding of these interactions will be critical to the development of microbiome-informed, personalized approaches to melanoma management and immunotherapy optimization.