title: Temporal Stability in Chronic Wound Microbiota Is Associated With Poor Healing.
abstract: Microbial burden of chronic wounds is believed to play an important role in impaired healing and the development of infection-related complications. However, clinical cultures have little predictive value of wound outcomes, and culture-independent studies have been limited by cross-sectional design and small cohort size. We systematically evaluated the temporal dynamics of the microbiota colonizing diabetic foot ulcers, a common and costly complication of diabetes, and its association with healing and clinical complications. Dirichlet multinomial mixture modeling, Markov chain analysis, and mixed-effect models were used to investigate shifts in the microbiota over time and their associations with healing. Here we show, to our knowledge, previously unreported temporal dynamics of the chronic wound microbiome. Microbiota community instability was associated with faster healing and improved outcomes. Diabetic foot ulcer microbiota were found to exist in one of four community types that experienced frequent and nonrandom transitions. Transition patterns and frequencies were associated with healing time. Exposure to systemic antibiotics destabilized the wound microbiota, rather than altering overall diversity or relative abundance of specific taxa. This study provides evidence that the dynamic wound microbiome is indicative of clinical outcomes and may be a valuable guide for personalized management and treatment of chronic wounds.
authors: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Michael
authors: M
authors: Loesche
authors: University of Iowa, College of Nursing, Iowa City, Iowa, USA. Electronic address: sue-gardner@uiowa.edu.
authors: Sue E
authors: SE
authors: Gardner
authors: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Lindsay
authors: L
authors: Kalan
authors: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Joseph
authors: J
authors: Horwinski
authors: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Qi
authors: Q
authors: Zheng
authors: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Brendan P
authors: BP
authors: Hodkinson
authors: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Amanda S
authors: AS
authors: Tyldsley
authors: Comprehensive Access and Delivery Research and Evaluation (CADRE) Center, Iowa City VA Health Care System, Iowa City, Iowa, USA.
authors: Carrie L
authors: CL
authors: Franciscus
authors: Departments of Radiology and Biostatistics, University of Iowa, Iowa City, Iowa, USA.
authors: Stephen L
authors: SL
authors: Hillis
authors: Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Samir
authors: S
authors: Mehta
authors: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Departments of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: David J
authors: DJ
authors: Margolis
authors: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: egrice@upenn.edu.
authors: Elizabeth A
authors: EA
authors: Grice
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D017719:Diabetic Foot / Q000188:drug therapy* / Q000382:microbiology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008390:Markov Chains; D064307:Microbiota / Q000187:drug effects*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents