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Title: Analysis of the microbiome and host-transcriptome in psoriasis and atopic dermatitis
Author: Muirhead, Gareth Sion
ISNI:       0000 0004 8499 8719
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2017
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Skin is the primary interface to the external environment, protecting us from harmful compounds and infection. Over many millennia, coevolution has culminated in a mutualistic relationship between ourselves and a specialised, yet diverse resident community of microorganisms. This microbiota is thought to exist in a delicate balance to maintain homeostatic equilibrium, and plays a role in the shaping of our immune system. Skin diseases are some of the most common human disorders and present a considerable economic burden. There is now growing appreciation of the role the cutaneous microbiome plays in disease, and how host-microbe interplay is associated with disorders of the immune system. The cutaneous microbiota as well as the host transcriptome and the interactions between them is the focus of this thesis. Computational methods were used to examine the microbiota and transcriptomes of a large cohort of matched samples from healthy volunteers and patients with Atopic Dermatitis (AD) and Psoriasis (PSO). The community composition of inflamed and healthy skin was assessed and the specific species which are over-represented on diseased skin were identified. In parallel, the host gene expression was pro led to identify common and disease specific transcriptional signatures revealing clinically relevant pathways. Next, using schemes of dimensionality reduction and computational methods, the associations between microbes, disease severity and host transcription was interrogated. Staphylococcus aureus demonstrated an impressive relationship with AD associated gene signatures, whereas host-microbe associations in PSO were inconclusive. Using Weighted Gene Co-expression Networks Analysis (WGCNA), gene-gene interaction networks were reconstructed and differentially connected modules between healthy and inflammatory states were identified. Modules encoding processes for the epidermal barrier, extracellular matrix, non-coding RNA metabolism and immune system processes were all associated with the relative abundance of S. aureus. Overall, whilst associations in psoriasis were inconclusive, a range of host-microbe interactions were uncovered in AD. The results presented in this thesis contribute towards a greater understanding of the differences in the cutaneous microbiome and the transcriptional mechanisms which underlie allergic and autoimmune inflammation.
Supervisor: Tsoka, Sophia ; Nestle, Frank Oliver Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available