Examining diabetic heel ulcers through an ecological lens: microbial community dynamics associated with healing and infection

Purpose While some microorganisms, such as Staphylococcus aureus, are clearly implicated in causing tissue damage in diabetic foot ulcers, our knowledge of the contribution of the entire microbiome to clinical outcomes is limited. We profiled the microbiome of a longitudinal sample series of 28 people with diabetes and ulcers of the heel in an attempt to better characterise the relationship between healing, infection and the microbiome. Methodology 237 samples were analysed from 28 ulcers, collected at fortnightly intervals for six months or until healing. Microbiome profiles were generated by 16S rRNA analysis, supplemented by targeted nanopore sequencing. Key findings Ulcers which failed to heal during the study period were more likely to be persistently colonised with a diverse community of microorganisms including anaerobes and Enterobacteriaceae (diversity 2.2 healed (n=8) vs. 3.1 unhealed (n=20), p<0.001). During clinically apparent infection, a reduction in the diversity of microorganisms in an ulcer was often observed due to expansion of one or two taxa, with recovery in diversity at resolution. Modelling of the predicted species interactions in a single ulcer with high diversity indicated that networks of metabolic interactions may exist that contribute to the formation of stable communities. Conclusion Longitudinal profiling is an essential tool for improving our understanding of the microbiology of chronic wounds, as community dynamics associated with clinical events can only be identified by examining changes over multiple time points. The development of complex communities, particularly involving Enterobacteriaceae and strict anaerobes, may be contributing to poor outcomes and requires further investigation.