Histopathological Changes Induced by Malassezin: A Novel Natural Microbiome Indole for Treatment of Facial Hyperpigmentation

Background: Malassezin is a natural indole compound produced by the fungus Malassezia furfur and preclinical investigations have demonstrated an ability to suppress melanogenesis. Objective: To investigate the histopathological effects of malassezin for treatment of facial hyperpigmentation. Methods: In this proof-of-concept study, seven subjects with facial hyperpigmentation caused by melasma or photodamage applied topical malassezin twice daily for 14 weeks, followed by eight weeks of observation. At baseline, 2 mm punch biopsies were taken from hyperpigmented areas and adjacent uninvolved skin. Skin biopsies from hyperpigmented areas were repeated at 8, 14, and 22 weeks. Paraffin-embedded sections were cut and stained with H&E, Fontana Masson, and MART 1 and assessed for histopathological changes. Results: Increased epidermal melanin and dermal melanophages were observed in all biopsies at baseline in the hyperpigmented compared to uninvolved skin of all subjects. Eight and 14 week biopsies of involved skin revealed decreased epidermal melanin in all subjects treated with malassezin. Melanocytes appeared less dendritic compared to baseline, and numbers were slightly reduced at eight weeks. Biopsies at 22 weeks showed no significant difference in epidermal melanin levels compared to baseline hyperpigmented skin, and melanocytes were comparable in number and dendricity to baseline. There was no evidence of melanocyte atypia in any of the biopsies. These features were similar in melasma and photo-damaged skin. Conclusion: This study documents the histopathological features and ability of malassezin, a novel agent unique to the skin microbiome, to decrease epidermal pigmentation and the temporary and revisable nature of the process.