Human Skin Microbiome: Integrating bacterial, fungal and viral communities
Authors: Segre Julie , Kong Heidi , Tirosh Osnat , Byrd Allyson 
Published: June 2021

The varied topography of human skin offers a unique opportunity to study how the body's microenvironments influence the functional and taxonomic composition of microbial communities. The general accessibility of skin also enables longitudinal clinical studies throughout the course of disease manifestations. Metagenomic analysis of diverse body sites in healthy humans defined the skin microbiome as shaped by local biogeography yet marked by strong individuality. We identified strain‐level variation of dominant species as heterogeneous and multiphyletic. Re‐sampling months and years later revealed that despite the skin's exposure to the external environment, its bacterial, fungal, and viral communities were largely stable over time. Strain and single nucleotide variant level analysis showed that individuals maintain, rather than reacquire prevalent microbes from the environment.Longitudinal stability of skin microbial communities generates hypotheses about colonization resistance and empowers clinical studies exploring alterations observed in disease states, such as the inflammatory skin disorder atopic dermatitis (AD; commonly known as eczema). Integrating shotgun metagenomic sequencing, culturing, and animal models, we explored a model whereby staphylococcal strains contribute to AD disease exacerbation. This delineation of highly individualized skin microbiomes with patient‐specific strains underscores the individuality of the disease course and therapeutic response in AD patients and may represent an opportunity for precision medicine.Although landmark studies have shown that microbiota activate and educate host immunity, how the immune system shapes microbial communities and contributes to disease is less‐well characterized. We explore the skin microbiome of patients with primary immune deficiencies to address this question and to expand our understanding of microbes that colonize human skin. Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility5. DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen‐dense tissues, such as skin6. Analyzing deep metagenomic sequencing data from DOCK8‐deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity as compared to healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8‐deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.Support or Funding InformationNHGRI, NIAMS, NCI, NIAID, NIH Intramural Research ProgramThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.