Identifying Probiotic Bacteria By Modeling Time Trends For Mice With Chronic And Non-chronic Wounds
Samantha VanSchalkwyk, Jane H. Kim, Paul Ruegger, James Borneman, Daniel Jeske, Manuela Martins-Green.
University of California, Riverside, Riverside, CA, USA.
There is a critical need to heal diabetic chronic wounds. A major contributor to non-healing of diabetic ulcers is the presence of biofilm. However, current treatments cannot eradicate biofilm because the etiology of biofilm initiation and development is poorly understood. In the studies presented here we used next generation sequencing and our db/db-/- model of chronic wounds, which naturally develops biofilm when we raise the levels of oxidative stress in the wound right after wounding. We identified bacteria in the microbiome of these chronic wounds from wounding to 20d post-wounding when the wounds are fully chronic to determine how the composition of the microbiome evolves and how it differs from that found in non-chronic wound at comparable times. We then used this longitudinal repeated measures dataset from chronic or non-chronic wounds, to identify bacteria that have differing time trends in the two groups for the purpose of identifying probiotics. A statistical model is fit through Generalized Estimating Equations (GEE), and then a test is performed for interaction between group and time with generalized score statistics. This interaction test is done for each of the bacteria, and significant tests indicate that the trend of counts differs for the chronic and the non-chronic group over time. When the interaction test is significant, probiotics are identified as those bacteria that have increasing time trends in the non-chronic group and flat or decreasing time trends in the chronic group. Bacteria of interest as possible probiotics are for example Propionibacterium sp. The identification of probiotic bacteria that can be used for treatment of chronic wounds is novel and could potentially contribute to the development of novel approaches for the treatment of diabetic foot ulcers.
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