The dynamic wound microbiome

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The dynamic wound microbiome Chunan Liu1,2, Alise J. Ponsero1,2, David G. Armstrong3, Benjamin A. Lipsky4,5 and Bonnie L. Hurwitz1,2*

Abstract Background: Diabetic foot ulcers (DFUs) account for the majority of all limb amputations and hospitalizations due to diabetes complications. With 30 million cases of diabetes in the USA and 500,000 new diagnoses each year, DFUs are a growing health problem. Diabetes patients with limb amputations have high postoperative mortality, a high rate of secondary amputation, prolonged inpatient hospital stays, and a high incidence of re-hospitalization. DFU-associated amputations constitute a significant burden on healthcare resources that cost more than 10 billion dollars per year. Currently, there is no way to identify wounds that will heal versus those that will become severely infected and require amputation. Main body: Accurate identification of causative pathogens in diabetic foot ulcers is a critical component of effective treatment. Compared to traditional culture-based methods, advanced sequencing technologies provide more comprehensive and unbiased profiling on wound microbiome with a higher taxonomic resolution, as well as functional annotation such as virulence and antibiotic resistance. In this review, we summarize the latest developments in defining the microbiology of diabetic foot ulcers that have been unveiled by sequencing technologies and discuss both the future promises and current limitations of these approaches. In particular, we highlight the temporal patterns and system dynamics in the diabetic foot microbiome monitored and measured during wound progression and medical intervention, and explore the feasibility of molecular diagnostics in clinics. Conclusion: Molecular tests conducted during weekly office visits to clean and examine DFUs would allow clinicians to offer personalized treatment and antibiotic therapy. Personalized wound management could reduce healthcare costs, improve quality of life for patients, and recoup lost productivity that is important not only to the patient, but also to healthcare payers and providers. These efforts could also improve antibiotic stewardship and control the rise of “superbugs” vital to global health. Keywords: Diabetic foot ulcer, Wound microbiome, Metagenomics, Next-generation sequencing

Background Chronic wounds are a common complication of diabetes mellitus that can severely affect a patient’s quality of life and may lead to lower limb amputation [1–5]. The 5-year mortality for diabetic foot ulcers (DFUs), and minor and major amputations was recently reported to be 30.5, 46.2, and 56.6% [6]. In particular, foot ulcers are prevalent in patients with * Correspondence: [email protected] 1 Department of Biosystems Engineering, University of Arizona, Tucson, AZ, USA 2 BIO5 Institute, University of Arizona, Tucson, AZ, USA Full list of author information is available at the end of the article

long-standing diabetes, mostly related to peripheral neuropathy and ischemia from peripheral vascul