Shotgun-lipidomics reveals disease specific microbiome-lipid correlations in acne vulgaris and atopic dermatitis

Skin surface lipids and commensal skin microbes are integral constituents of the epidermal barrier; however, the mutual interaction of both components has not been comprehensively studied. With the oily and dry skin condition of acne vulgaris (AV) and atopic dermatitis (AD), respectively, two prototypical chronic inflammatory skin diseases as well as matched healthy skin were used to identify lipid-microbial correlations in health and disease. To this end, mass spectrometry based high- resolution shotgun lipidomics of epidermal tape strips was performed and results were coupled to 16S amplicon sequencing data of the skin microbiome. Disease- specific lipids and microbes were identified for both lesional and non-lesional skin samples and interaction networks of microbes and lipids were built. While both AD and AV were characterized by different set of specific connections of microbes and lipids, respectively, a clear trend towards microbe centric modular structures from healthy over non-lesional to lesional skin was seen in both AD and AV indicating higher specificity of microbe and lipid relationship in lesional stage whereas in healthy the relashionship is more diverse. In line with the observed mutual antagonism of S. hominis and NdS 18:0;2/24:0;0 lipid in vivo, in vitro inoculation of S. hominis led to decrease of NdS 18:0;2/24:0;0 lipid and was associated with reduction of pro- inflammatory mediators in reconstructed human epidermis. Thus, in addition to the known direct impact at skin immunity, skin-colonizing microbes specifically shape the lipid structure of the epidermis