A multiomics approach to identify host-microbe alterations associated with infection severity in diabetic foot infections: a pilot study

Diabetic foot infections (DFIs) are a major cause of hospitalization and can lead to lower extremity amputation. In this pilot study, we used a multiomics approach to explore the host-microbe complex within DFIs. We observed minimal differences in the overall microbial composition between PEDIS infection severities, however Staphylococcus aureus and Streptococcus genera were abundant and highly active in most mild to moderate DFIs. Further, we identified the significant enrichment of several virulence factors associated with infection pathogenicity belonging to both Staphylococcus aureus and Streptococcus. In severe DFIs, patients demonstrated a greater microbial diversity and differential gene expression demonstrated the enrichment of multispecies virulence genes suggestive of a complex polymicrobial infection. The host response in patients with severe DFIs was also significantly different as compared to mild to moderate DFIs. This was attributed to the enrichment of host genes associated with inflammation, acute phase response, cell stress and broad immune-related responses, while those associated with wound healing and myogenesis were significantly depleted.

Automated summary

This study investigated the host-microbe complex within DFIs using a multiomics approach, identifying Staphylococcus aureus and Streptococcus as abundant and highly active. Patients with severe DFIs demonstrated greater microbial diversity, enrichment of multispecies virulence genes, and significant differences in host response compared to mild to moderate DFIs.