The skin microbiome: current perspectives and future challenges

Abstract

Complex communities of bacteria, fungi, and viruses thrive on our skin. The composition of these communities depends on skin characteristics, such as sebaceous gland concentration, moisture content, and temperature, as well as on host genetics and exogenous environmental factors. Recent metagenomic studies have uncovered a surprising diversity within these ecosystems and have fostered a new view of commensal organisms as playing a much larger role in immune modulation and epithelial health than previously expected. Understanding microbe-host interactions and discovering the factors that drive microbial colonization will help us understand the pathogenesis of skin diseases and develop new promicrobial and antimicrobial therapeutics.

Figure 1. Metagenomics is a culture-free method to assess skin microbiota

(A) DNA is purified directly from a skin swab or biopsy. This DNA contains a mixture of genomic DNA from skin and microbial cells. PCR is used to amplify all bacterial DNA with primers that anneal to the conserved region of the 16S rRNA gene. Then, these PCR amplicons are sequenced. Finally, sequences can phylogenetically classified to give the species identities within the microbiome and sequences can be counted to give relative abundances of each species. (B) An alignment of the 16S rRNA gene between S. aureus and S. epidermidis downloaded from NCBI and aligned via Geneious (http://www.geneious.com/). Blue lines show nucleotides that differ between the two species. Inset shows an example of the specific sequence differences.

Figure 2. Composition of a single metagenome

(A) Phylogenetic tree of an example metagenome downloaded from MG-RAST (data from Fierer et al). The number of sequences in the metagenome that correspond to each phylogenetic category is listed. For example, 3790 sequences making up 62% of the metagenome's sequences were found to be Actinobacteria by similarity to references sequences. (B) Pie chart showing microbial composition within the same example metagenome. Chart was generated using Krona on the MG-RAST website (http://metagenomics.anl.gov/).

Figure 3. Microbiome composition on normal human skin

Sebaceous (blue text), moist (orange text), and dry (green text) habitats are labeled anatomically. Microbial composition differs among the habitats (pie charts at right). The four major phyla are shown: Actinobacteria, Firmicutes, Proteobacteri, and Bacteroidetes. Within these phyla, the three most abundant genera are also shown: Propionibacterium, Corynebacterium, and Staphylococcus. Figure is compiled with data pooled from many metagenomes, from Grice et al. Figure is adapted from Figure 3 in Grice et al with permission from Nature Publishing Group.

Figure 4. The microbiome and skin immunology

Viruses, bacteria, and fungi (purple, red, or green dots) cover human skin and its appendages. Keratinocytes produce antimicrobial peptides (AMPs). Sebocytes produce free fatty acids (FFAs). Some commensal microbes also produce AMPs and FFAs, as well as pheno-soluble modulins (PSMs). These molecules all inhibit pathogen colonization. Commensal microbes may additionally inhibit pathogen growth by competition and crowding on the skin surface. The microbiota also interact with immune cells to activate them or modulate their production of pro- and anti-inflammatory cytokines. Backbone skin diagram downloaded from Docstoc (www.docstoc.com).