The role of the microbiome in diabetic foot ulcers: Biofilm community dynamics differ with healing outcomes

Diabetic foot ulcers often develop into non-healing chronic wounds due to their high risk of infection resulting from exposure to various microbes, combined with a lowered immune response due to the patient's diabetic status. Recently, an increased understanding of the polymicrobial nature of chronic wound infections has given rise to questions on the role of the microbiome on healing outcomes. In our study, we aimed to investigate the microbiome composition and its pathological influence in 128 patients using the Oxford NanoPore Sequencing platform and the 16S rRNA region for sample amplification. Overall, the most abundant genera and species present in the microbiomes of these patients resembled other published studies, namely Cutibacteria, Staphylococcus and Pseudomonas. A key factor in healing outcomes was the presence of fungi, which was strongly correlated with pathogenic anaerobes such as Prevotella bivia and associated with negative outcomes. While we could not determine a direct causal link between fungi and outcomes, the data strongly suggests that fungal presence plays a role in the composition of bacterial communities in the wound environment and is potentially enabling infection persistence. Furthermore, we observed that certain bacterial species were present in all outcomes, but part of different microbial networks, hinting that healing success could be determined by these associations established in the community rather than presence of a specific pathobiont. In conclusion, while an initial look at the composition can provide an insight into the most abundant genus/species present in certain outcomes, when investigating deeper we see that associations among different taxa may play a more significant role in determining healing. We postulate that interfering with these interactions could potentially be the key to tipping the balance towards positive healing outcomes.