Skin Microbiota in Atopic Dermatitis

Abstract

The skin microbiota represents an ecosystem composed of numerous microbial species interacting with each other, as well as with host epithelial and immune cells. The microbiota provides health benefits to the host by supporting essential functions of the skin and inhibiting colonization with pathogens. However, the disturbance of the microbial balance can result in dysbiosis and promote skin diseases, such as atopic dermatitis (AD). This review provides a current overview of the skin microbiota involvement in AD and its complex interplay with host immune response mechanisms, as well as novel therapeutic strategies for treating AD focused on restoring skin microbial homeostasis.

Keywords: atopic dermatitis; dysbiosis; skin microbiota.

Figure 1

Schematic representation of human skin structure consisting of three main layers: epidermis, dermis and subcutis. The outermost skin layer, epidermis, is composed of terminally differentiated keratinocytes that enable continuous skin renewing, held together by corneodesmosomes and mortar lipids. Epidermis is supported by the collagen-bound dermis that provides a home for nerves, blood, lymph vessels, mast cells and other structures (i.e., sweat glands, hair follicles), and subcutis consisting of adipose tissue. Skin regions vary in terms of topography, temperature, salt content and acidity (pH) and are, based on their features, categorized into three major groups: moist sebaceous and dry.

Figure 2

Epithelial barrier dysfunction, immune dysregulation and skin microbiota dysbiosis in initiation and progression of AD. Epithelial barrier dysfunction and stress from environmental and mechanical factors lead to skin barrier damage and enhanced epidermal permeability, which in turn increases microbial and allergen contact with the cutaneous immune system. Damaged keratinocytes activate immune mechanisms by releasing proinflammatory cytokines (IL-1β, TSLP, IL-25, IL-33) and chemokines, mobilizing innate lymphocyte subsets and skin-resident dendritic cells (DCs). DCs attract and prime naive T-cells, promoting T_H2/T_H22 cell responses and inducing inflammation process. Type 2 cytokines (IL-4, IL-5, IL-13, IL-25) drive the inflammation, recruiting and activating other types of immune cells, such as eosinophils, mast cells and B-cells. The secreted molecules and proinflammatory cytokines act directly on cutaneous nerves and contribute to pruritus. Moreover, the inflammation further disrupts skin barrier and favors colonization by pathogens (S. aureus), additionally inducing keratinocyte damage and boosting T_H2-type response, thus supporting the disease cycle. The activation of T_H1/T_H17 cell responses in chronic disease induce tissue remodeling, increasing skin thickness and lichenification. IDEC—inflammatory dendritic epidermal cell, ILC2—group 2 innate lymphoid cell, LC—Langerhans cell, T_H1—T_H1 cell, T_H2—T_H2 cell, T_H17—T_H17 cell, T_H22—T_H22 cell.

Figure 3

Comparison of microbiota composition between healthy skin and skin affected by AD.

Figure 4

Interplay between Staphylococcus aureus and skin microbiota. Several members of Staphylococcus genus inhibit S. aureus growth and biofilm formation. Staphylococcus lugdunensis and S. hominis suppress colonization of S. aureus by secreting antibiotics and lantibiotics. S. epidermidis induces keratinocytes to produce anti-microbial peptides (AMPs) to eradicate S. aureus, as well as produces protease glutamyl endopeptidase (Esp) which inhibits formation of S. aureus biofilm. The MgSAP1 protease secreted by Malassezia globosa was shown to have a similar effect of disrupting S. aureus biofilm. In contrast, Cutibacterium acnes and its corpoporphyrin III molecule promote S. aureus activity and aggregation, thus inducing S. aureus biofilm formation.