# Skin Lipid–Microbe Interplay Links Staphylococcus hominis to Barrier Control in Adult Atopic Dermatitis

## TL;DR

The study finds that a specific skin bacterium, Staphylococcus hominis, influences lipid levels and inflammation in atopic dermatitis, suggesting a role in skin barrier function.

## Contribution

The paper identifies Staphylococcus hominis as a key regulator of lipid-microbe interactions in atopic dermatitis through multi-omics analysis and functional validation.

## Key findings

- Lesional AD skin shows less diverse lipid-microbe interactions compared to non-lesional and healthy skin.
- Staphylococcus hominis negatively correlates with specific sphingolipids and positively with diacylglycerols in AD skin.
- In vitro experiments confirm S. hominis reduces inflammation and alters lipid metabolism in reconstructed human epidermis.

## Abstract

Skin surface lipids and commensal microbes are essential for the epidermal barrier, but their mutual interactions remain poorly understood.

We conducted high‐resolution shotgun lipidomics of tape strips from lesional and non‐lesional atopic dermatitis (AD) skin and healthy controls. Lipidomic data were integrated with 16S amplicon sequencing to construct lipid–microbe interaction networks.

AD skin showed disease‐specific lipid–microbe correlations, with less diverse interactions in lesional compared to non‐lesional and healthy skin.
Staphylococcus hominis
(
S. hominis
) negatively correlated with non‐hydroxy—dehydrosphingosine (NdS) 18:0;2/24:0;0 and positively with diacylglycerol (DAG) 18:1;0_18:1;0 and DAG 16:0;0_18:1;0. In vitro co‐cultures of reconstructed human epidermis (RHE) with AD skin‐derived T cell supernatant (TCS) and S. hominis reduced RHE thickness, spongiosis, and NdS 18:0;2/24:0;0 levels. Furthermore,
S. hominis
directly lowered NdS 18:0;2/24:0;0 levels in lesional AD skin tape samples, and reversed type 2 inflammation and lipid metabolism gene expression in TCS‐stimulated RHE.

These findings identify
S. hominis
as a key regulator of lipid–microbe interactions in AD, influencing epidermal inflammation and differentiation.

This study investigates mutual interaction of skin microbes and surface lipids in AD using the advanced method of shotgun lipidomics with ultra‐broad coverage of lipids and 16S amplicon sequencing of tape strips taken from lesional and non‐lesional AD and healthy controls. Multi‐omics integration of microbiome and lipidome from lesional and non‐lesional AD as well as healthy skin reveals disease‐specific interaction networks. S. hominis correlates with key lipid species and functional validation in RHE and bacterial culture models confirms S. hominis as a regulator of skin lipid homeostasis. Abbreviations: AD, atopic dermatitis; DAG, diacylglycerol; LS, lesional; NdS, non‐hydroxy–dehydrosphingosine; NL, non‐lesional; RHE, reconstructed human epidermis; RNAseq, RNA sequencing; S. hominis, Staphylococcus hominis; TCS, T cell supernatant; US, unstimulated.