Mathematical modelling of the roles of microbiome in pathogenesis of atopic dermatitis

Atopic dermatitis (AD) is the most common inflammatory skin disease. Due to the lack of
understanding of the pathophysiology of the disease, current treatment strategies merely manage
symptoms, and there is no curative or preventative treatment. Given the globally increasing
prevalence of this disease, and high cost of therapies for severe AD, it is important to design
preventative treatment strategies, rather than applying expensive therapies regularly over the lifetime
of patients with this chronic disease. The aim of this research project is to understand the role of skin
microbiome in AD pathogenesis and then derive treatment strategies capable of preventing the
emergence of AD or treating the symptoms in those who have already developed it.

The aim of this research is to understand the role of the skin microbiome in pathogenesis of AD and
then suggest primary and secondary prevention strategies. We will approach this by developing and
analysing a systems-level mathematical model of the skin microbiome and aetiology of AD. This aim
is separated into two parts, directed at primary prevention (preventing allergic sensitisation which
prcedes AD), and secondary prevention (preventing AD early in development to prevent it from
becoming chronic or difficult to control) (Figure 2).
The term "allergic sensitisation" refers to the training of an adaptive immune response to react to an
antigen, specifically the production of immunoglobulin E (IgE) antibodies, and thereby the induction
of atopic disease. In atopic diseases, the host adaptive immune response becomes skewed towards
inflammatory responses [18], and blood serum IgE is increased [19, 20], which is a hallmark of atopic
disease, and of severe AD [21].
This project has two main objectives, which correspond to primary and secondary disease
prevention:
Objective 1: To identify what changes in microbiome could be responsible for triggering allergic
sensitisation AD.
Objective 2: To identify what changes in microbiome or immune response could be responsible for
triggering AD flares.