Developing Human Skin Microbiota Models to Replace Rodent Studies and Explore Host-Microbe Interactions

Our vision is to develop human wound microbiota and infection models that can suitably replace, and substantially improve upon, currently available rodent microbiota/infection models. We will combine our human ex vivo skin platform with a novel curated clinical biobank of skin/wound bacteria to deliver methodology that will be state-of-the-art but also widely adoptable. This new human-centric model will provide fundamental insights into the characteristics of bacteria that lead to poor healing in the clinic, identifying important therapeutic targets. Finally, we will work with a dermatology-focused industrial partner to demonstrate the feasibility of our human ex vivo skin microbiota/infection models for targeted antimicrobial testing, confirming commercial and clinical suitability. This research will deliver a robust and transformative animal replacement platform to enable human-focussed, predictive outputs from host-microbiome and antimicrobial testing studies.

Our proposal builds upon pioneering new research demonstrating how the skin’s microbial community, or microbiota, is linked to wound infection and clinical outcome. Our group were the first to reveal that the bacterial profile of human chronic skin wounds predicts whether they will heal, and it is now clear that certain types of bacteria lead to poor healing when tested in mice. Despite these important findings, understanding of the role of the skin microbiota in human wound infection and pathology is still in its infancy. This is because currently used murine skin and wound microbiota/infection models show poor translational applicability to humans. Moreover, current state-of-the-art non-animal models fail to recapitulate the complex architecture, physiology and microbiota of human skin.

Non-animal skin/wound microbiome models are greatly needed to translate research into clinical outcomes. Chronic, non-healing wounds remain an area of significant unmet need, costing the National Health Service a staggering £8.2Bn per year to treat. Many wounds still fail to heal even with best practice care, with infection preceding up to 90% of wound-related limb amputations. Thus, validated and predictive human models have significant potential to drive 3Rs and societal impact.

Our approach will succeed as we have assembled a world-leading team, unique resources and the tools to deliver a substantially improved translational model, meeting important academic and commercial demand. Our expertise spans skin biology, microbiology and infection, with a track-record of developing novel models, supported by established clinical and commercial partnerships. We will facilitate wide adoption of our platform through our leading translational wound centre, working with national and international stakeholders to provide access to expertise and resources.