Skin microbiome analysis of a junctional epidermolysis bullosa patient treated with genetically modified stem cells

Junctional epidermolysis bullosa (JEB) is a subtype of epidermolysis bullosa caused by mutations in the LAMB3 gene. We treated a patient with JEB using genetically corrected autologous epidermal cultures retrovirally transduced with the functional LAMB3 gene sequence. The objective of this study was to analyze the skin microbiome of this patient, with a particular focus on transgenic skin, and to compare the findings to the skin microbiome of healthy controls and patients with atopic dermatitis and well-documented microbial dysbiosis.

Skin microbiome analysis was performed on a JEB patient 72 months after combined gene and stem cell therapy. Skin swabs from age-matched healthy controls and atopic dermatitis patients were included from the ProRaD study of CK-CARE.

The transgenic skin had comparably high relative and absolute Staphylococcus (S.) aureus abundance to blistering and non-blistering skin of the JEB patient, while the total bacterial load was lower. In blistering skin of the JEB patient, higher bacterial load was driven by S. aureus.

Our investigation confirms a unique microbiome composition in JEB, characterized by S. aureus driven bacterial overgrowth. The dysbiosis was not reversed in transgenic, non-blistering skin areas. However, the transgenic skin demonstrates stability in an environment of bacterial dysbiosis.