Anaerobe-associated microbial shifts at infection onset in diabetes-related foot ulcers revealed by longitudinal metagenomics

<h4>Introduction</h4>Diabetes-related foot infections (DRFIs) are a major cause of hospitalisation and carry a significantly increased risk of lower extremity amputation. To date there is a lack of longitudinal studies examining within-patient microbiome dynamics during the transition from non-infected to infected diabetes-related foot ulcers (DRFUs).<h4>Methods</h4>We used shotgun metagenomic sequencing to longitudinally profile the wound microbiome of 6 patients with DRFUs who developed clinical infections, utilising taxonomic profiling, metagenome assembly and binning and strain level analysis to characterise within-patient microbial shifts.<h4>Results</h4>DRFUs with no signs of clinical infection were colonised by virulent pathogens including <i>Staphylococcus aureus, Streptococcus agalactiae, Enterococcus faecalis, Enterobacter hormaechei</i> and <i>Pseudomonas aeruginosa</i>. In most patients, infection onset was associated with a decrease in pathogen abundance and a significant increase in obligate anaerobes including <i>Prevotella</i> spp, <i>Peptoniphilus</i> spp, <i>Porphyromonas</i> spp and <i>Anaerococcus</i> spp.<h4>Conclusion</h4>These findings highlight the potential importance of anaerobes and hypoxia in DRFIs and may support monitoring of tissue oxygen saturation as a predictor of infection onset.