Skin Microbiome of Monogenic Skin Disorders - PROJECT SUMMARY / ABSTRACT
Ichthyosis describes the dry, scaly skin that results from different genetic disorders that alter different
constituents of the skin barrier. In all forms of ichthyosis major changes occur in the quality, quantity and
function of the stratum corneum, the soil on which the microbiome grows. Common phenotypic features of the
ichthyoses include scaly skin, increased trans-epidermal water loss (TEWL), and reduced stratum corneum
water content. However, significant biochemical differences will also exist depending on the genotype of the
ichthyosis. In turn, these biochemical differences are likely determinants of the skin microbiome. The goal of
our proposal is to understand the effect of the skin microenvironment on microbial colonization and dynamics
through the study of monogenic human skin disorders. We will first, compare the skin microbiome of
individuals with genetically distinct ichthyoses with healthy individuals, testing the null hypothesis that
the skin microbiome in all individuals with ichthyosis is the same, regardless of the genetic cause of their
ichthyosis, but will be different from that of healthy skin. We will recruit 10 individuals each from five distinctive
genetic diagnoses and 20 gender and age-matched healthy controls. Performing metagenomic shotgun
sequencing, we will compare microbial diversity, composition, and microbial biochemical pathways with
genotype to identify differences between ichthyotic and healthy skin and between patient cohorts. This will
identify microbes that possess metabolic pathways that may be associated with the unique biochemical
substrate created by each deficiency. Second, we will correlate the ichthyotic skin microbiome with
phenotypic features to determine microbial associations with skin environment, because biochemical
differences in the stratum corneum resulting from the different mutations may not be the critical determinant of
the microbiome. Therefore, we will test the null hypothesis that the skin microbiome in all individuals with
ichthyosis is the same regardless of the underlying biochemical manifestation of their disease, but is
dependent on skin characteristics. We will identify correlates such as diversity, composition, and microbial
biochemical pathways with phenotypic characteristics, such as lamellar vs. keratodermic scale, inflammation,
TEWL defects, temperature, pH from the different patient cohorts and controls. These correlates may explain
interactions that are phenotype rather than genotype-specific. This project will provide basic insights into
whether the skin microbiome of ichthyotic skin is modified by the biochemical differences in the stratum
corneum due to monogenic skin disorders, or if the ichthyotic environment is the dominant determinant of the
skin microbiome.
