The Airway Microbiome After Burn and Inhalation Injury Public Deposited

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Last Modified
  • March 20, 2019
Creator
  • Walsh, Dana
    • Affiliation: School of Medicine, Curriculum in Toxicology
Abstract
  • The human microbiome is composed of the entirety of microorganisms living on and in the human body along with their genetic material. Recent work has demonstrated the importance of these bacterial communities, or microbiota, in health and disease, including in the airways. Though the airways contain mechanisms to clear bacteria, disruption of homeostasis by illness and injury can induce conditions favorable to bacterial colonization and growth. Inhalation injury endured by burn victims disrupts homeostasis by damaging the airway epithelium and inhibiting innate immune responses, increasing the risk of acute respiratory distress syndrome (ARDS), infection, and pneumonia. Inhalation injury is a known cause of ARDS, which is partly diagnosed by hypoxia in the airways as indicated by a PaO2/FiO2 ratio ≤ 300. There is a known link between ARDS and bacterial infection in the airways, but the relationship is complex and poorly understood. Diagnosis of airway bacterial infection in this patient population can be challenging due to limitations in detecting and identifying the colonizing organism. The goal of this dissertation research was to identify differences in the airway microbiota among patients with PaO2/FiO2 ratios ≤ 300 and > 300 after experiencing burn and inhalation injury. Bacterial DNA was extracted from therapeutic bronchial washings of patients hospitalized for burn and inhalation injury at the North Carolina Jaycee Burn Center and sequenced. Patients with PaO2/FiO2 ratio ≤ 300 demonstrated increases in low-abundance bacteria as well as significant enrichment of Prevotella melaninogenica that was not altered by antibiotic treatment. Bacterial taxa among patients with PaO2/FiO2 ratio ≤ 300 were grouped into correlation networks that were distinct both in composition and predicted function from patients with PaO2/FiO2 ratio > 300. Further, predicted functions important in characterizing the communities were unique for each disease state, identifying changes in bacterial interactions and functional roles that may be important in progression of hypoxia and ARDS. This combination of metagenomics with advanced computational analyses allows identification of specific changes relevant to the entire community, providing focused hypotheses for further validation and investigation that may lead to new therapeutic targets for preventing bacterial infection after burn and inhalation injury.
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Rights statement
  • In Copyright
Advisor
  • Diaz-Sanchez, David
  • Muhlebach, Marianne
  • Jaspers, Ilona
  • Cotter, Peggy
  • Randell, Scott
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
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