Shotgun Metagenomic Investigation of the Microbiome in Diabetic Foot Infections Compared to Healthy Skin

Diabetic foot infection (DFI) is a major complication of diabetes, causing significant morbidity and mortality. Host factors and microorganisms in DFI can disrupt healing processes, leading to chronic, non-healing wounds. The aim of this study was to characterise the microbiome of DFIs and contralateral healthy foot skin (CHFS). Thirty-two diabetic patients were enrolled in this study. Samples were obtained from DFIs and CHFS from the same patient. The microbiome was profiled using metagenomic shotgun sequencing. All the samples were polymicrobial, with a predominance of the obligate anaerobes belonging to Bacteroidetes in PEDIS 4. While PEDIS 3 and 2 were dominated by Proteobacteria. CHFS showed similar bacterial composition across all grades of severity, and the most abundant genera detected were Corynebacterium, Staphylococcus, Pseudomonas, and Cutibacterium. The CHFS was more diverse than DFIs in PEDIS 3 and 4. However, DFIs and CHFS in PEDIS 2 present similar diversity. In addition, DFIs of this grade exhibited a high proportion of Corynebacterium as well as CHFS. PCoA analysis demonstrated that the community structure of DFIs was different from that of CHFS, with Prevotella, Bacteroides, and Porphyromonas the main contributors to the clustering. Neighbour-Net analyses revealed that DFIs exhibited lower diversity compared to CHFS and harboured a more homogeneous dominant bacterial community. Our study revealed a high abundance of obligate anaerobes, including Bacteroides, Prevotella, Morganella, and Porphyromonas, in more severe infections; along with a decrease in microbial diversity. Additionally, there was a decrease in the abundance of key bacteria from the normal skin microbiota.