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THE INFLUENCE OF THE GUT MICROBIOME ON BONE AND JOINT DISEASE

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Abstract

Osteoporosis and osteoarthritis are among the most common musculoskeletal disorders in the United States. Osteoporosis and osteoarthritis can result in pain, loss of motion or structural support, and/or impaired activities of daily living. The gut microbiome has been associated with the pathogenesis of a number of diseases including osteoarthritis and osteoporosis. However, the role of the gut microbiome in bone and joint disease is largely understudied. Previous studies demonstrate that alterations to the microbiome are linked to changes in bone quantity and quality, but the specific microbial components that change bone are not known. We selectively removed components of the gut microbiota to identify microbial communities responsible for changes in bone. Impaired tissue strength was associated with a reduction in the capacity to synthesize microbe-derived vitamin K, a greater abundance of Firmicutes, and decreased abundance of Actinobacteria, Proteobacteria, and Verrucomicrobia when compared to animals with unaltered tissue strength. We have previously shown that alterations to the microbiome throughout growth reduce the bone strength at skeletal maturity due to changes in tissue quality. However, it is unclear if disruption of the gut microbiome alters all bone tissue or only affects bone tissue at the time of formation. Here we tested the idea that alterations to the gut microbiome influence bone at the time of formation by disrupting the microbiome at different stages of growth and determining bone strength at skeletal maturity. Alterations to the gut microbiome during a period of more rapid bone growth resulted in more pronounced decreases in tissue strength, suggesting that disruption of the microbiome influences bone at the time of tissue formation. Recent studies have shown that diet-induced obesity and associated alterations to the microbiome enhance the severity of post-traumatic osteoarthritis. Previous studies of obesity and osteoarthritis involve fracture or surgical trauma that cause local inflammatory responses and can contribute to cartilage loss, but fracture or surgical trauma are not seen in most osteoarthritis patients. In this thesis we characterized the effect of obesity and the accompanying changes of the gut microbiome on the severity of post-traumatic osteoarthritis in the absence of fracture or surgical trauma. Our results demonstrated that severe and mild obesity do not enhance cartilage degeneration, suggesting limited effects of obesity on post-traumatic osteoarthritis generated without severe damage to surrounding tissues as seen with surgery/fracture. Together, this work sets the foundation for future discoveries relating the microbiome to bone and joint disease and contributes to the ultimate goal of using the gut microbiome as a therapeutic to reduce the severity and prevalence of musculoskeletal diseases.

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156 pages

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Date Issued

2020-08

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Bone; Bone Strength; Cartilage; Gut Microbiome; Orthopaedics; Post-traumatic Osteoarthritis

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Hernandez, Professor, Christopher J.

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Brito, Ilana Lauren
van der Meulen, Marjolein

Degree Discipline

Mechanical Engineering

Degree Name

Ph. D., Mechanical Engineering

Degree Level

Doctor of Philosophy

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Government Document

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dissertation or thesis

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