PCR primers and variable regions for taxonomic classi cation af- ter high-throughput sequencing of the PCR products.6,7 Another crucial point is that there is no international standardization for sampling methods. Because of this, comparisons between dif- ferent papers can be biased due to the sampling method, the variable 16S rRNA region used, and sometimes by the databases used. Standardization of sampling methods remains a key prob- lem in comparing results from different studies. Composition Molecular methods arising from advances in genomic technology have permitted a detailed description of the skin microbiota.6,8-11 Bacteria on the skin are from four main bacterial phyla, Actino- bacteria, Firmicutes, Proteobacteria, and Bacteroidetes, and the three most common genera are Corynebacteria, Propionibacteria, and Staphylococci.12 The microbiota of the skin varies across its surface, and four main "environments" have been described: 1) Moist (the axilla, the inner elbow, or the inguinal fold), harbor- ing mostly Staphylococci and Corynebacteria12; 2) Sebaceous (the forehead, the malar crease, the retroauricular crease, and the back), having a higher density of Propionibacteria13,14; 3) Dry (eg, the upper buttock area), hosting predominantly Staphylococci, Propionibacteria, Micrococci, Corynebacteria, Enhydrobacter, and Streptococci15; and 4) Others (sweat glands or hair follicles), host- ing facultative anaerobes, such as Propionibacterium spp.12,16,8 The distribution of follicles, eccrine, apocrine, and sebaceous glands contribute to the variable cutaneous microenvironments as do skin pH, moisture, and temperature. This likely selects subsets of bacteria that can thrive in each ecosystem.17 Factors Influencing Bacterial Growth The skin provides a “culture medium” for the growth of bac- teria. These microorganisms require water, sources of carbon, nitrogen, and macro-, and microelements. Water is crucial to microbial growth on the skin, and the amount of water avail- able to support this growth is referred to as water activity (aw). Water activity varies from 0 (no free water available) to 1.0 (all molecules of water are free).18 Water activity strongly in uences the growth of microorganisms and differs consider- ably between the main environments of human skin described above.16 Staphylococcus aureus is able to grow until aw of 0.83, Staphylococcus epidermidis is less resistant (unable to grow below aw of 0.87), and Pseudomonas uorescens is unable to grow below aw of 0.97. Dry skin therefore favors growth of potentially invasive Staphylococci and inhibits the growth of commensal organisms. Thus, moisturizers play two important roles in the barrier function of the skin: 1) Preservation of the physical barrier; and 2) Maintenance of the normal composition of the skin microbiota. of the cutaneous bacterial ora are said to be in uenced by gender, age, and ethnicity. Climate, ultraviolet radiation, pol- lution, and lifestyle factors including diet, hygiene habits, and drug and alcohol consumption may also in uence the compo- sition of the skin microbiota.19-27 STRUCTURE AND FUNCTION OF THE SKIN BARRIER The skin barrier, as well as the microbiota, protects the body against a wide range of external dangers. This barrier consists of the epidermis and several layers below it that in uence function and harbor microbes.3,28,29 The physical barrier of the skin is formed mainly by the stratum corneum, which is composed of dead keratinocytes or corneocytes and proteinaceous crosslinking laments.30,31 The corneocytes are surrounded by a proteinaceous structure called the corni ed envelope. This structure consists of a layer of highly crosslinked insoluble proteins covalently bound to a layer of lipids. The lipid matrix forms the main permeability barrier against the invasion of bac- teria and other hazardous substances.31-33 Filaggrin ( lament aggregating protein) also contributes to the barrier function of the epidermis.The breakdown of laggrin results in the produc- tion of alanine, pyrrolidone carboxylic acid, and urocanic acid, which act as natural moisturizers in the stratum corneum and lower skin surface pH. Histidine released from laggrin deg- radation provides protection against ultraviolet light.33,32 The S-100 calcium binding domain in the molecular structure of pro laggrin may play a role in calcium signaling.33 Nucleated keratinocytes in the stratum granulosum and stra- tum spinosum form cell–cell adhesion junctions that also contribute to barrier function.30,31 Importantly, the condition of the epidermal barrier depends on physical properties that in- clude the amount of sebum produced, hydration, and pH.30 The skin also has a chemical barrier that is comprised of defense molecules that are expressed constitutively or induced and can either directly inhibit microbial growth or serve as activators and mediators of the innate and adaptive immune responses.34 Kera- tinocytes protect against infection via the innate production and release of antimicrobial peptides (AMPs).These molecules, which are also produced by mast cells, neutrophils, and sebocytes, pro- vide innate microbicidal action against infectious pathogens (as opposed to antibiotics which have more of a static, or inhibitory, effect). Some AMPs (eg, cathelicidin) also function by triggering in ammatory cell recruitment and cytokine release.35,36 AMPs can be produced constitutively, or actively induced by proin am- matory cytokines or signaling from pattern recognition receptors (eg, Toll-like receptors [TLRs]).35 Role of Skin Microbiota in Protection from Infection and Inflammation It is becoming increasingly accepted that commensal species of microorganisms that naturally reside on the surface of the The skin’s bacterial landscape is highly dynamic with both the composition and relative abundance of bacteria varying considerably across individuals. The diversity and abundance
