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

Introduction 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). Methods 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. Results DRFUs with no signs of clinical infection were colonised by virulent pathogens including Staphylococcus aureus, Streptococcus agalactiae, Enterococcus faecalis, Enterobacter hormaechei and Pseudomonas aeruginosa . In most patients, infection onset was associated with a decrease in pathogen abundance and a significant increase in obligate anaerobes including Prevotella spp, Peptoniphilus spp, Porphyromonas spp and Anaerococcus spp. Conclusion 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.