The Microbiome and the Human Immune Response in Atopic Dermatitis : Exploring Microbial Targets for Personalized Treatment

Atopic dermatitis (AD) is a common chronic inflammatory skin disease. An impaired skin barrier and altered immune mechanisms are considered the two major players in AD inflammation. Alterations in the microbiome are an established finding in AD, but its role in the pathogenesis is still poorly understood. In this thesis we primarily aimed to characterize the microbial composition of the skin, nose and gut in pediatric patients with mild to severe AD. Our second aim was to estimate the prevalence of Staphylococcus (S.) aureus in patients with AD and to study the humoral immune response against S. aureus. Additionally, we designed a clinical study to test the effect of a new endolysin-based therapy that specifically targets S. aureus in AD. The results of the research described in this thesis show the relevance of the microbiome, in particular S. aureus in AD. The thesis describes associations between S. aureus, but also other microbes on the skin and in the nose with AD disease severity. Thereby, S. aureus seems to evoke immune responses via different mechanisms, as a directly stimulating antigen and as an allergen. The results of this thesis may contribute to the development of treatment strategies that target the microbiome in AD. Further prospective cohort studies and experimental research are needed to clarify the role of the microbiome in AD.

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