High Levels of Oxidative Stress and the Skin Microbiota Contribute Towards Initiation and Development of Chronic Wounds in Diabetic Mice
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High Levels of Oxidative Stress and the Skin Microbiota Contribute Towards Initiation and Development of Chronic Wounds in Diabetic Mice

Abstract

The skin is the largest organ of the human body. It is barrier that defends and protects the body against environmental assaults and has the important role in maintaining physiological homeostasis, functioning as a highly regulated interface between the outside and inside of the body. Residing on the skin is a microbial community known as the skin microbiota which consists of bacteria, fungi, and viruses. These microbes residing in specific niches of the skin interact with each other and potentially impact the health of the skin through crucial skin-microbe interactions. Research on the resident skin microbiota is ongoing; however, current research suggests that beneficial microbes, commensal microbes, and pathogens all have a role in maintaining healthy skin or causing infection and disease in the skin. When the skin is injured, the human body activates the cutaneous wound healing process to close the wound as quickly and thoroughly as possible to re-establish the protective and defensive roles of the skin. Skin of healthy individuals will heal quickly; however, skin that is afflicted with oxidative stress or inflammation may not heal in a timely manner. When healing is delayed for any number of reasons, the wound may develop into a chronic wound. Chronic wounds are defined as wounds with prolonged healing time greater than four weeks and have very high risk of chronic infections which in turn can further increase healing time. Infected chronic wounds are colonized by bacteria and fungi which can form biofilm, polymeric structures that protect the microbes from the immune system and prolong the infection of the pathogenic microbes. Chronic wounds are difficult to heal as the biofilm present on the wounds are recalcitrant to conventional antimicrobial therapies including antibiotics. To understand how chronic wounds are initiated and what role bacteria play on the skin, I employed a novel chronic wound model in obese, diabetic mice previously developed in our lab. Using this model, I studied how levels of oxidative stress is crucial for the initiation and development of chronic wounds. The level of oxidative stress stimulates bacteria in the wound to produce biofilm soon after injury. I also used to model to study the community of the bacteria that reside on healing and chronic wounds over time. I show that the diversity of the bacteria in healing wounds is very diverse while chronic wounds which also contain biofilms are not. I identified bacterial species associated with either healing wounds or wounds. Lastly, I provide a review on the importance of bacteria in healthy skin, ailing skin and chronic wounds. Taken together, my finding show that oxidative stress is crucial for the initiation and development for chronic wounds and the biofilm that infect them. Further research on the wound-microbe interaction is required to understand the underlying mechanisms that lead to the development of chronic wounds. This knowledge will lead to the discovery and development of new therapies that can heal and prevent chronic wounds.

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