Skin microbiota - metabolome signatures in atopic dermatitis associated with staphylococcus aureus and commensal bacteria

Summary: Abstract Body: Introduction and Aim: Staphylococcus aureus (SA) skin infections are common in atopic dermatitis (AD) driving flares and chronicity, while commensal bacteria such as Staphylococcus epidermidis (SE) and Corynebacterium are reduced in severe AD. We aimed to identify associations between the skin microbiome and metabolome, to examine metabolite-mediated host-microbiome interactions in AD. Methods: Skin microbiome and metabolome swabs were obtained from adults with mild-severe AD (n=11). Shotgun metagenomic sequencing and nuclear magnetic resonance spectroscopy quantified the microbiome and metabolome, respectively. Machine learning data integration was used to identify interactions between the microbiome and metabolome. Results: Individual variability in microbiome diversity as well as SA, SE and Corynebacterium relative abundance is high in this cohort and no significant differences between lesional and non-lesional AD were observed. However, the skin metabolome profile is altered in lesional AD, with increased glucose metabolism products, proline, alanine and branched chain amino acids (BCAA). In AD samples with high SA abundance, these metabolites are increased further. AD samples with a high abundance of the skin commensals SE or Corynebacterium are both associated with increased natural moisturizing factor (NMF) components urocanic acid, pyroglutamic acid, citrulline and histidine (correlation coefficient >0.55). Conclusions: Distinct metabolic signatures are associated with SA and skin commensal species in AD and may underlie novel host-microbiome interactions. BCAA are important SA nutrients and promote its virulence factors alpha-toxin, hyaluronidase, and Panton–Valentine leucocidin. In contrast the commensal-associated metabolome signature may protect the skin barrier through NMF production. Helen Alexander^{2, 1}, Alphonsus Yip^{2, 1}, Yi Yang¹, Jose Garcia Guevara¹, Xin Yi Ng¹, Adrien Le Guennec¹, David Moyes¹, Saeed Shoaie¹, Catherine Smith^{2, 1}, Richard Woolf², Alessandra Vigilante^{2, 1}, Carsten Flohr^{2, 1} 1. King's College London, London, England, United Kingdom. 2. St John's Institute of Dermatology, London, England, United Kingdom. Innate Immunity, Microbiology, and Microbiome