Early melanoma invasivity correlates with gut fungal and bacterial profiles

Background The microbiome is emerging as a crucial player of the immune checkpoint in cancer. Melanoma is a highly immunogenic tumour, and the gut microbiome composition has been correlated to prognosis and evolution of advanced melanoma and proposed as biomarker for immune checkpoint therapy. Objectives We investigated the gut fungal and bacterial composition in early-stage melanoma and correlated microbial profiles with histopathological features. Methods Bacterial 16S rRNA and fungal ITS region sequencing was performed from faecal samples of patients affected by stage I and II melanoma, and healthy controls. A meta-analysis with gut microbiota data from metastatic melanoma patients was also carried out. Results We found a combination of gut fungal and bacterial profiles significantly discriminating M patients from controls. In melanoma patients, we observed an abundance of Prevotella copri and yeasts belonging to the Saccharomycetales order. We found bacterial and fungal community correlated to melanoma invasiveness, whereas specific fungal profile correlated to melanoma regression. Bacteroides was identified as general marker of immunogenicity, being shared by regressive and invasive melanoma. In addition, the bacterial community from stage I and II patients were different in structure and richer than those from metastatic melanoma patients. Conclusions Gut microbiota composition in early-stage melanoma changes along the gradient from in situ to invasive (and metastatic) melanoma. Changes in the microbiota and mycobiota are correlated to the histological features of early-stage melanoma, and to the clinical course and response to immune therapies of advanced stage melanoma, through a direct or indirect immunomodulation.