Topical Oxygen Therapy Shifts Microbiome Dynamics in Chronic Diabetic Foot Ulcers

Authors: Paul Hunter, BSc; Elisa Greco, MD; Karen Cross, MD, PhD; and Julie Perry, PhD

Citation: Hunter, P., Greco, E., Cross, K., Perry, J., 2020. Topical oxygen therapy shifts microbiome dynamics in chronic diabetic foot ulcers. Wounds: a compendium of clinical research and practice, 32(3), 81–85.

Keywords: microbiome, biofilm, diabetic foot ulcer, DFUs, exudate, topical oxygen, what to expect

This study aims to determine the mechanism of action of NATROX® O₂ topical oxygen wound therapy in diabetic foot ulcers by examining the diversity of bacterial genera present in DFUs treated with topical oxygen therapy.

Abstract Introduction: Bacterial biofilm in wounds prevents healing by acting as a physical barrier to wound closure and hyperactivating local inflammatory processes, thus making its removal a high priority. The authors previously have shown that adding topical oxygen to standard wound care increased healing of Texas Grade II and III diabetic foot ulcers (DFUs), which they hypothesized was a result of alterations of the wound microbiome/biofilm. Objective. This study aims to determine the mechanism of action of topical oxygen in DFUs by examining the diversity of bacterial genera present in DFUs treated with topical oxygen. Materials and Methods. Six patients with chronic DFUs had their wounds swabbed weekly over an 8-week period of continuous topical oxygen treatment, and microbiome diversity was assessed by metagenomic 16S rDNA sequencing using a next-generation sequencing platform. Results. The wound microbiome shifted toward a diverse flora dominated by aerobes and facultative anaerobes with oxygen therapy in 5 healed wounds. In contrast, anaerobic flora persisted in a single nonhealing ulcer in the present study cohort. Conclusions. Although the sample size was small, this study suggests topical oxygen therapy may have the ability to encourage the growth of aerobic members of the wound microbiome and be an effective alternative to antibiotics in this area.

Key points:

  • Although the sample size is small, because this is scientific work, the results are more impartial and therefore of greater significance than clinical data with similar sample sizes. The data doesn’t rely on subjective measurements such as “the wound is improving, it’s less painful”. DNA sequencing can’t be skewed.
  • Skin microbiome is generally of mix species and acts to protect us from pathogenic bacteria.
  • In the presence of a wound, the microbiome can form a biofilm which affects 60-100% of chronic wounds and prevent wound closure.
  • DFUs have a very different microbiome which empowers opportunistic pathogens, making them more susceptible to issues.
  • Fig. 1 demonstrates the reduction in wound size.
  • 4 of the 6 patients demonstrated an increase in wound size in the first 2 weeks of therapy. One of the wounds that didn’t increase also didn’t heal.
  • Fig. 2 demonstrates the difference between a responder and non-responder to NATROX® O₂ by comparing their 16s rDNA sequencing.
  • Fig. 3 gives greater detail of the bacteria present with 16s rDNA testing was completed weekly.
  • The only patient showing no change is Patient 2, the non-responder.
  • As the bacteria significantly changes (normally around week 2), the change seems to be linked to the increase in exudate and wound size.
  • All the wounds that progressed on to complete wound healing demonstrated significant changes to their microbiome over the NATROX® O₂ therapy period.
  • Table 2 classifies the main bacteria identified during the study.
  • Fig. 5 amalgamates the class of microbe across all patients during oxygen therapy. As the wounds show clinical signs of healing, there is a clear transition from a flora dominated by anaerobes to a flora rich in aerobic species.