66 TESTING
Selection of study subjects with rational inclusion/exclusion criteria
Hypothesis
Choice of appropriate control(s) if necessary
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Whole Genome Shotgun sequencing
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16S amplicon sequencing
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Figure 2: Conducting a microbiome study step by step: 1) sampling of skin microbial community; 2) extraction of DNA; 3) amplification and sequencing using the 16S-based approach or Whole Genome Shotgun (WGS) metagenomic sequencing; 4) taxonomic classification, community composition and functions.
bacterial species are Propionibacterium acnes, Staphylococcus epidermis, Corynebacterium spp. The majority of fungal species are yeasts from the genus Malassezia. The majority of the microorganisms of the skin microbiota are commensal.
The chemical milieu of the skin varies with the anatomical area. Some areas of the body are dry, some areas are moist whereas other areas with a high density of sebaceous glands are enriched in lipids. These different micro-environments promote the growth of different microorganisms. Thus oily skin predominantly hosts lipophilic Propionibacteria, Staphylococci and Malassezia species. Moist skin areas such as armpits, inguinal creases, inner elbows are dominated by Staphylococci and Corynebacteria. Dry areas harbour a mixed population of bacteria with a greater prevalence of β-Proteobacteria and Flavobacteriales. In addition to the anatomical area and chemical milieu, any other factors shape the composition of the cutaneous microbiota: sex, age, lifestyle, personal hygiene and washing practices, immune status, presence of skin diseases, and geography. Therefore there is a very wide inter-subject variation in the composition of the skin microbiota although physiologically comparable skin sites contain similar bacterial communities. The differences in community composition can be measured thanks to the microbiota alpha- and beta- diversities which compare a specific area of the body to other areas of the same individual and a specific area of the body between different individuals respectively. From the early idea that microbes were
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either potential threats to human health or some kind of parasites exploiting their hosts for nutrients, a new concept has progressively emerged where the skin microbiota acts as partner for maintaining proper functions of the healthy skin. To date several functions in skin health have been attributed to the main skin commensal microorganisms. The Gram-positive Staphylococous epidermis produces anti- microbial peptides and bacteriocins which can inhibit the colonisation of the skin by pathogens. Another function of S. epidermis concerns the regulation and promotion of the host inflammatory response. The Gram-positive lipophilic Propionibacterium acnes contributes to the maintenance of a healthy skin by metabolising sebum triglycerides to short chain fatty acids which exhibit anti-microbial properties protecting against invading pathogens such as Staphylococcus aureus and Streptococcus pyogenes, and by keeping the acidic skin mantle. The lipophilic yeast Malassezia degrades sebum and one of the by-products from fatty acid degradation is azelaic acid which also has anti-microbial activity. Skin resident commensals such as S. epidermis and P. acnes contribute to the regulation of the immune response and can modulate inflammatory responses by recruiting and activating particular cells in the skin. Recent research indicates that bacterial diversity and the relative abundance of different microbes, present on and in the skin, may contribute to the integrity of the barrier function of the stratum corneum and in the maintenance of homeostasis. Tissue repair is also influenced by the microbiome of the skin.
When the normal skin microbiota experiences a perturbation (dysbiosis),
aberrant immune responses, cutaneous inflammation and disease may develop. Although the causality link is usually difficult to establish, changes in the skin microbiota clearly play a role in the pathogenesis of some skin diseases and skin disorders. Shifts in skin bacterial and fungal communities have been linked to a number of skin diseases and conditions. Thus clinical microbiological and dermatological studies have reproducibly pointed to the strong associations between P. acnes and Acne vulgaris, S. aureus and atopic dermatitis, Malassezia and dandruffs. Changes in the bacterial composition of the skin have also been linked to psoriasis or rosacea and recent researches have raised the possibility that the cutaneous microbiome may contribute to the pathogenesis of bullous pemphigoid, one of the most common autoimmune blistering diseases. Explaining the pathophysiology or etiology of these skin diseases is not the scope of this article. It is sufficient to mention that the occurrence, the severity of the diseases and skin conditions are generally associated either to a loss of microorganisms diversity or to a change in the abundance of particular bacterial species.
Designing skin microbiome studies Similarly to all clinical studies, the key factors for a successful skin microbiome study are a clear initial hypothesis with a well formulated question and the selection of clinically and biologically important outcome variables. This is particularly important in the field of microbiome research since important questions such as the causality relationship between the composition of one microbiota and the occurrence of a particular skin problem are often not fully answered. Compliance with Good Clinical Practices
September 2018
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