P09 Skin microbiota: metabolome signatures in atopic dermatitis associated with <i>Staphylococcus aureus</i> and <i>Staphylococcus epidermidis</i>

Abstract Introduction and aims Skin infections with Staphylococcus aureus are common in atopic dermatitis (AD) and drive disease flares and chronicity. In contrast, commensal Staphylococci such as Staphylococcus epidermidis are reduced in severe AD and reduce skin inflammation. The mechanisms underlying the host–microbiome interactions in AD remain poorly understood. The skin microbiota is highly metabolically active and microbial metabolites may have immunoregulatory functions in AD. The aim of this project was to identify associations between the skin microbiome and metabolome in order to examine metabolite-mediated host–microbiome interactions in AD. Methods Skin microbiome and metabolome swabs were obtained from adults with mild-to-severe AD (n = 11). The skin microbiome was quantified through shotgun metagenomic sequencing, and the skin metabolome was profiled using nuclear magnetic resonance spectroscopy. Machine learning data integration methods were used to identify interactions between the microbiome and metabolome in AD. Results Individual variability in skin microbiome diversity as well as S. aureus and S. epidermidis relative abundance is high in this cohort and no significant differences between lesional and nonlesional AD were observed. However, the skin metabolome profile is altered in lesional AD, with increased glucose metabolism products, branched chain amino acids (BCAAs) as well as the amino acids proline and alanine. In AD samples in which S. aureus is highly abundant, these metabolites are increased further. AD samples with a high abundance of S. epidermidis are associated with increased levels of natural moisturizing factor (NMF) components urocanic acid, pyroglutamic acid, citrulline and histidine (correlation coefficient &amp;gt; 0.55). Conclusions Distinct metabolic signatures are associated with S. aureus and S. epidermidis in AD and may underlie novel host–microbiome interactions in the disease. BCAAs are important S. aureus nutrients and promote its virulence factors alpha-toxin, hyaluronidase, and Panton–Valentine leucocidin. In contrast, the commensal S. epidermidis-associated metabolome signature may protect the skin barrier through NMF production.