Metabolomic Analysis of Skin Biopsies from Patients with Atopic Dermatitis Reveals Hallmarks of Inflammation, Disrupted Barrier Function and Oxidative Stress

Abstract

The main objectives of this study were to characterize the metabolomic profile of lesional skin of patients with atopic dermatitis, and to compare it with non- lesional skin of patients with atopic dermatitis and skin of controls with no dermatological disease. Skin-punch biopsies were collected from 15 patients and 17 controls. Targeted analysis of 188 metabolites was conducted. A total of 77 metabolites and their ratios were found, which differed significantly between lesional skin of atopic dermatitis, non-lesional skin of atopic dermatitis and skin of controls. The metabolites were members of the following classes: amino acids, biogenic amines, acylcarnitines, sphingomyelins or phosphatidylcholines, and the most significant differences be-tween the groups compared were in the concentrations of putrescine, SM.C26.0 and SM.C26.1. The alterations in metabolite levels indicate inflammation, impaired barrier function, and susceptibility to oxidative stress in atopic skin.

Keywords: biomarkers; dermatology; meta­bolomics; atopic dermatitis.

Fig. 1

Boxplots of concentrations of 6 metabolites which were statistically significantly (Kruskal–Wallis rank sum test, Benjamini–Hochberg (false discovery rate; FDR 5%) corrected p-value < 0.05) different between atopic dermatitis lesional skin (AD-L), atopic dermatitis non-lesional skin (AD-NL) and the skin of controls (C). The levels are reported as micromolar (μM) concentrations. (A) Putrescine; (B) SM.C26.0, sphingomyeline C26:0; (C) SM.C26.1, sphingomyeline C26:1; (D) PC.aa.C32.0, phosphatidylcholine diacyl C32 :0 ; (E) PC. aa. C40. 5, phosphatidylcholine diacyl C40:5; (F) PC.aa.C42.5, phosphatidylcholine diacyl C42:5.

Fig. 2

Principal component analysis (PCA) plot based on the whole dataset from targeted analysis. Red circles: atopic dermatitis lesional skin (AD-L) skin samples; blue squares: atopic dermatitis non-lesional skin (AD-NL) skin samples; green triangles: C skin samples. X and Y axes represent percentage of variability. x axis: Principal Component 1: 41.1% explained variance; y axis: Principal Component 2: 11.4% explained variance.