Microbiome of the Skin and Gut in Atopic Dermatitis (AD): Understanding the Pathophysiology and Finding Novel Management Strategies

Jung Eun Kim, Hei Sung Kim, Jung Eun Kim, Hei Sung Kim

Abstract

Atopic dermatitis (AD) is a long-standing inflammatory skin disease that is highly prevalent worldwide. Multiple factors contribute to AD, with genetics as well as the environment affecting disease development. Although AD shows signs of skin barrier defect and immunological deviation, the mechanism underlying AD is not well understood, and AD treatment is often very difficult. There is substantial data that AD patients have a disturbed microbial composition and lack microbial diversity in their skin and gut compared to controls, which contributes to disease onset and atopic march. It is not clear whether microbial change in AD is an outcome of barrier defect or the cause of barrier dysfunction and inflammation. However, a cross-talk between commensals and the immune system is now noticed, and their alteration is believed to affect the maturation of innate and adaptive immunity during early life. The novel concept of modifying skin and gut microbiome by applying moisturizers that contain nonpathogenic biomass or probiotic supplementation during early years may be a preventive and therapeutic option in high risk groups, but currently lacks evidence. This review discusses the nature of the skin and gut flora in AD, possible mechanisms of skin-gut interaction, and the therapeutic implications of microbiome correction in AD.

Keywords: atopic dermatitis; gut; microbiome; microbiota; skin; therapeutic implications.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Epidermal barrier disruption in AD skin. Trans-epidermal water loss (TEWL), pH, serum IgE, serum thymus and activated cytokine (TARC/CCL17), and eosinophils are significantly elevated in AD patients. Filaggrin and stratum corneum (SC) lipid composition, and serine protease (Kallikreins) are also altered in AD, allowing S. aureus colonization. With the decrease in coagulase-negative Staphylococci (CoNS) and its antimicrobial peptides (AMP), S. aureus proliferates and also forms biofilms. AD: Atopic dermatitis; CER: Ceramide; FFA: Free fatty acid; IL: Interleukin; S. aureus: Staphylococcus aureus; TNF: Tumor necrosis factor; TSLP: Thymic stromal lymphopoietin.
Figure 2
Figure 2
The complex interaction between the environment and the host. High microbial diversity associated with vaginal delivery, breast feeding, interaction with siblings and pets increases regulatory T cells (Treg), short chain fatty acids (SCFAs), and immune tolerance. Low biodiversity early in life affects the host immune system which is likely to cause a proinflammatory response. Intervention with pre/pro- and synbiotics and vitamin D may favorably influence the intestinal environment. IgE: Immunoglobulin E; IL: Interleukin; Th2: T helper 2 cells.
Figure 3
Figure 3
Muscosal barrier disruption in AD. Patients with AD have dysbiosis and less short-chain fatty acids (SCFAs) in the gut. In response to pro-inflammatory cytokines, monocytes migrate and differentiate into macrophages. Greater access to luminal antigen also causes T cells to transform into Th2 cells in the draining lymph nodes. Immunoglobuin E (Ig E) and mast cells are also more abundant in the lamina propria. IgE: Immunoglobulin E; IL: Interleukin; Th2: T helper 2 cells; TSLP: Thymic stromal lymphopoietin; IgA: Immunoglobulin A.
Figure 4
Figure 4
Immune mechanisms of pre- and probiotics. Prebiotics feed the commensal bacteria and protiotics. Probiotics modulate the humoral response (increase IgA and decrease IgE), balance cell-mediated immune response (increase Treg cells and decrease Th2 response), compete with pathogens, and modify the microenvironment. SCFA: short chain fatty acid; AMP: anti-microbial peptide; DC: Dendritic cell; IL: Interleukin; TGF: Tumor growth factor; IgE: Immunoglobulin E; IgA: Immunoglobulin A; Th1: T helper 1 cells; Th2: T helper 2 cells.
Figure 5
Figure 5
Vitamin D controls autophagy and the production of antimicrobial peptides which can help normalize the microbiota. It also regulates innate and adaptive immunity in various ways.

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