EVALUATION OF GUT MICROBIOTA IN MELANOMA AND VITILIGO PATIENTS

Several investigations have disclosed the association of gut dysbiosis with cancer development and pointed out the active role of a specific gut microbial signature in strongly regulating anticancer immune surveillance. A plethora of evidences also reveal a gut dysbiosis in patients affected by autoimmune disorders and suggest that microbes inhabiting the human gastrointestinal tract can modulate both innate and adaptive systemic immune responses. Achromic macules resembling vitiligo (an autoimmune disorder) (melanoma associated leukoderma, MAL), sometimes occur in melanoma patients because of an autoimmune response toward melanoma antigens shared by normal melanocytes and are significantly associated with a better prognosis in advanced stages. No studies have been performed so far to evaluate bacterial and fungal gut microbiota composition in early melanoma patients, whereas only two studies assessed gut bacterial microbiota in advanced melanoma patients treated with immunological targeted therapy. As well, nothing is known about gut microbiota composition in patients developing MAL or vitiligo, neither at bacterial nor at fungal level. Aim of this study is to evaluate bacterial and fungal gut microbiota in melanoma patients and to compare such a microbiota with the one in patients affected by MAL or vitiligo. Since MAL is a rarely observed event, we could select as a comparison only vitiligo patients at present. Gut microbiota composition was investigated through next generation sequencing targeting bacterial 16S rRNA and fungal ITS in a group of patients affected by melanoma, vitiligo and properly matched healthy controls. Furthermore, this study evaluates possible associations between gut microbiota composition of melanoma and vitiligo patients and clinical and histopathological features of melanoma, or clinical, historical and serological features of vitiligo. In addition, a classical culture approach aiming to isolate fungi of melanoma faecal samples has been performed along with the metagenomic evaluation. Our results pointed out significant differences in the richness and relative abundance species of melanoma and vitiligo fungal gut microbiota, as compared to healthy controls. No significant difference in the richness and diversity was found on the contrary as regards to the bacterial microbiota. However, significant differences in the relative abundance of bacteria were observed between melanoma, vitiligo, and controls. Interestingly, the diversity of bacterial and fungal species was found to be influenced by specific prognostic histopathologic features of melanoma and clinical parameters of vitiligo. Overall, the results of this thesis underline the importance of fungal and bacterial evaluation in melanoma and vitiligo patients and suggest the need of future more in-depth evaluation aiming to identify possible therapeutic options.