Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients

Abstract

Cutaneous ichthyosis (CI) is a collective group of monogenetic disorders of cornification demonstrating epidermal scaling, fissuring, chronic skin inflammation, and increased susceptibility to infection. In healthy individuals the skin microbiome limits growth of pathogenic organisms; however, the microbiome signature in CI is poorly characterized. To rectify this, we investigated the microbiome signature across 7 subtypes of CI in 43 individuals of Southeast Asian ethnicity, of which exome sequencing revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis revealed distinct microbial populations, reduced commensal microbiota, and higher colonization by pathogenic species. This correlated with increased production of inflammatory cytokines, including Th17 and JAK/STAT signaling, in peripheral blood mononuclear cells. Moreover, we identified microbiota and inflammation alterations in wounds of CI patients responsible for impaired wound healing. Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI patients and provides critical information for improving therapeutic management.

Congenital Ichthyosis: A Practical Clinical Guide on Current Treatments and Future Perspectives

“…22 This finding is supported by investigations showing that multiple congenital ichthyosis subtypes harbor elevated JAK/STAT signaling. 23 With accessibility of the skin and monogenetic causes, ichthyosis has always been an obvious choice for gene therapy. Unfortunately, the few completed clinical trials have been disappointing, but they provided a framework for future potential gene therapy options.…”