Skin Microbiome in Disease States: Atopic Dermatitis and Immunodeficiency

Abstract

AbstractThe Human Microbiome Project seeks to explore the diversity of microbiota that resides in and on the human body, including the skin, in health and disease. The NIH Intramural Skin Microbiome Consortium (NISMC) is a trans-disciplinary group of experts engaged in the practice of genomics, bioinformatics, large-scale DNA sequencing, dermatology, immunology, allergy, infectious disease, and clinical microbiology. Atopic dermatitis (AD, “eczema”) is a chronic relapsing skin disorder that affects ~15% of U.S. children and is associated with $1 billion of medical costs annually. AD is characterized by dry, itchy skin, infiltrated with immune cells. Colonization by _Staphylococcus aureus_ (S. aureus) is ten-fold more common in AD patients and is associated with disease flares. We hypothesize that, in addition to S. aureus, AD may also be associated with additional microbes and/or selective shifts of commensal microbes that are relevant to disease progression. The NISMC seeks to define the microbiota that resides in and on the skin and nares of three patient groups, all of whom have eczematous lesions and are currently seen at the NIH Clinical Center: (1) AD patients; (2) Wiskott-Aldrich syndrome (WAS) patients; and (3) Hyper IgE syndrome (HIES) syndrome patients.Examination of the microbiome of patients with WAS or HIES syndromes, both rare immunodeficiencies, will advance our understanding of how an individual’s immune system shapes their cutaneous microbial community. We are performing a prospective longitudinal study that follows these groups of patient thorough the cycles of eczema flares, ascertaining clinical data and samples at each stage. To analyze the longitudinal samples obtained from both affected and unaffected skin sites, we will use an integrated approach including: (1) extensive characterization of bacterial diversity; (2) analysis of fungal diversity; (3) generation of whole-genome sequences of novel skin microbial isolates; and (4) metagenomic sequencing to assess microbial abundance and deduce metabolic activities. Examination of the microbial communities on affected and unaffected skin of patients with eczema will yield insights into the gene-environment interactions relevant to these diseases.