Topical Oxygen Therapy Shifts Microbiome Dynamics in Chronic Diabetic Foot Ulcers

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


Wounds. 2020;32(3):81-85. 

In This Article

Abstract and Introduction


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.


Human skin is normally colonized by a consortia of bacteria, fungi, and viruses (together referred to as the skin microbiome), which occupies this niche to prevent colonization of the skin by more pathogenic bacteria.[1] When a break in the skin occurs, members of the skin microbiome may colonize the wound as part of a developing wound biofilm. Although the clinical diagnosis of wound biofilm remains controversial, it is now recognized that biofilms are present in 60% to 100% of chronic wounds,[2–4] where they form a physical barrier to wound closure and maintain a state of chronic inflammation that can damage surrounding tissue.[4] Biofilm removal is therefore a therapeutic priority, but treatment options are limited due to the fact that biofilms are intrinsically tolerant to antibiotics.[5] The diabetic foot ulcer (DFU) microbiome is enriched in anaerobic bacteria when compared with other wounds[6] and harbors a greater number of opportunistic pathogens when compared with contralateral intact skin.[7] The abundance of anaerobes may be due to host factors (eg, poor tissue perfusion) but also may be inherent to the biofilm mode of growth.

Recognizing deep, 3-dimensional wounds are often anaerobic, the authors recently introduced a topical oxygen delivery device into their wound care practice with excellent clinical results.[8] The present study evaluated whether topical oxygen therapy (TOT) causes shifts in the wound microbiome from anaerobic species toward an aerobic community, thereby favoring healing. Given that the wound microbiome represents the building blocks of biofilm formation, understanding its composition and response to treatment is the first step toward improving treatment of biofilms in chronic wounds.