P29 Long-read sequencing provides unprecedented insight into the skin and wound microbial landscape

Abstract

Abstract Introduction and aims It is becoming increasingly evident that the microbial inhabitants of our skin play a key role in cutaneous health and disease. However, our understanding of the contribution of the complex skin microbiome to wound healing outcome remains incomplete. This is, in part, due to the historic challenges around traditional sampling and profiling Methods, which often fail to capture the abundance and diversity of the skin microbiome. Recent advances in microbiome sequencing technologies now enable more comprehensive characterization of skin bacterial composition and host-microbe interactions. Thus, the aim of this study was to utilize a novel long-read sequencing platform to provide species-level microbiome characterization and deliver important insight into the drivers of pathological skin repair. Methods Microbial DNA samples were collected from the skin and wounds of healthy volunteers and patients with chronic wounds (n = 40 per group). Long-read nanopore sequencing was used to profile microbiome samples, while RNA-Seq enabled generation of donor transcriptomic profiles. A multifaceted approach was used to integrate these datasets to investigate the complex interplay between host skin pathology and the microbiome. Results We first identified perturbations in the skin microbiome of patients with chronic wounds, which was significantly less diverse than healthy skin and colonized with key bacteria associated with pathogenicity. These alterations in the skin microbiome also correlated with transcriptomic changes, such as upregulation of genes associated with inflammation, stress and poor healing. Interestingly, long-read sequencing data displayed poor correlation with routine clinical microbiology swabs, while specific clinical characteristics (e.g. glycaemic control and wound duration) were strongly linked to wound microbiome composition. Conclusions Collectively, these data provide crucial new insight into the skin and wound microbial landscape, demonstrating a potential role for specific wound bacteria in modulating pathological skin repair.