An Overview of the Latest Metabolomics Studies on Atopic Eczema with New Directions for Study

Abstract

Atopic eczema (AE) is an inflammatory skin disorder affecting approximately 20% of children worldwide and early onset can lead to asthma and allergies. Currently, the mechanisms of the disease are not fully understood. Metabolomics, the analysis of small molecules in the skin produced by the host and microbes, opens a window to observe the mechanisms of the disease which then may lead to new drug targets for AE treatment. Here, we review the latest advances in AE metabolomics, highlighting both the lipid and non-lipid molecules, along with reviewing the metabolites currently known to reside in the skin.

Keywords: atopic dermatitis; atopic eczema; dermatitis; lipidomics; metabolomics; skin.

Figure 1

Model of AE development. The environment and the host could both drive the development of atopic eczema (AE). AE is characterized as having a disrupted skin barrier which could be induced through itching, filaggrin (FLG) mutation, and environmental exposures. The disruption then allows for oxygen to penetrate the skin, resulting in a decrease in the anaerobic microbiome and providing a new niche for bacterial growth. Microbial dysbiosis within AE could be a result of this niche, or could be the result of changing pH, salt levels, and/or other factors within the skin. This dysbiosis then provides the opportunity for S. aureus to overgrow. In addition, both scratching and allergens result in keratinocytes releasing cytokines, such as the thymic stromal lymphopoietin (TSLP). The cytokines then lead to the induction of a T-helper cell 2 (Th2) response through dendritic cell (DC) recruitment. AE non-lesional skin also has a thinner epidermis, allowing for easier penetration of allergens and irritants. These allergens can then activate mast cells (MC), resulting in the secretion of tryptase and histamine and thereby inducing itching.

Figure 2

Diagram of shorter-chain free fatty acids (SCFA) within atopic eczema. Free fatty acids are produced from the breakdown of the lamellar bodies [81,82], and the lysis of the skin’s proteins and sebum by Cutibacterium acnes [83,84], and a select few are produced by the microbiome under anoxic conditions by the fermentation of carbohydrates [85,86,87,88,89]. These free fatty acids contribute to the acidification of the skin, which in healthy individuals is around 4.7 [90]. This acidification discourages S. aureus growth, and the production of SCFAs inhibit the other growth of pathogenic sub-strains [79]. Resident skin bacteria can also use the SCFAs to interact with the host’s immune system through inducing T regulator cells (Tregs)—by decreasing the transcription of il6—and TSLP [91,92,93,94]. Studies in other organs suggest that SCFAs can inhibit dendritic cells’ expression of lipopolysaccharide-induced cytokines (IL-6 and IL-12p40) [95] and activate macrophages, neutrophils, and monocytes through the G-protein-coupled receptor FFAR2 [96]. Although well studied in other organ systems, the SCFAs’ mode of action in the skin is still unclear. Symbol: ↑ (increase) and a dotted arrow (theoretical mechanism).