The microbiome of the diabetic foot ulcer predicts clinical outcomes. human metagenome

Microbial burden of diabetic foot ulcers (DFUs), a common and costly complication of diabetes, is believed to play an important role in impaired healing and development of infection-related complications (i.e. wound deterioration, osteomyelitis, and amputation). We systematically evaluated whether the dynamic DFU microbiome is predictive of outcomes. Microbiota colonizing plantar DFUs (n=100) were collected every 2 weeks during a standardized treatment regimen. Culture-independent sequencing of the bacterial 16S ribosomal RNA gene was employed to assess multiple microbiomic metrics. DFUs clustered into four microbiome Community Types, largely defined by relative abundances of Staphylococcus and Streptococcaceae. Longitudinally, DFU microbiomes were dynamic and switched Community Types approximately every 3-4 weeks, and instability was associated with better outcomes. Microbiota measured at baseline was not predictive of healing or infection-related complication. Mixed logistic models incorporating longitudinal microbiomic data implicated Streptococcaceae in increasing odds of developing an infection-related complication and decreasing odds of healing. For DFUs that healed, when comparing microbiota at initial presentation to immediately prior to healing, Streptococcaceae decreased in relative abundance, while bacterial load increased. Our results demonstrate that aspects of the dynamic DFU microbiome are predictive of healing and infection-related complication, and may be a valuable guide for management and treatment efforts.