Airway Mechanics The Intestinal Microbiome And Their Interaction In Cystic Fibrosis Mouse Models

Airway Mechanics, the Intestinal Microbiome and Their Interaction in Cystic Fibrosis Mouse Models

"Cystic fibrosis (CF) is a severe, systemic disease that impacts multiple organs, including the lungs, bones and intestine. In the lungs, in addition to reoccurring cycles of infection and inflammation, a subset of CF patients present with airway hyperresponsiveness, the increased response of the airways to stimulus. In the intestine, CF patients present with obstructions, small intestinal bacterial overgrowth and an altered intestinal microbiome. In this thesis, we used CF mouse models, which recreate many of the CF clinical phenotypes, to investigate components of the CF disease, including the airway mechanics, intestinal disease and the intestinal microbiome. As dysbiosis of the intestinal microbiome has been recognized as an important contributing factor to many systemic diseases, we then investigated whether the murine CF intestinal microbiome influenced the CF lung, bone and intestinal disease. In the lungs, we investigated CF airway mechanics and showed that CF mice have a strain dependent airway hyperresponsiveness phenotype. In the intestine, we used 16S rRNA sequencing to show that CF mice have an altered intestinal microbiome, but each CF mouse model had a different dysbiosis. We also identified a correlation between bacterial load and intestinal circular muscle thickness. To determine the impact of the CF intestinal dysbiosis on systemic phenotypes, we treated CF mice with the antibiotic streptomycin. Streptomycin treatment reduced the CF bacterial overgrowth and altered the CF intestinal microbiome. These changes ameliorated the CF airway hyperresponsiveness, but did not influence the bone or intestinal disease. Further, we identified intestinal Lactobacillus overgrowth, plus components of the immune system, including Th17 lymphocytes and IL-17 producing [gamma][delta] T cells, as potentially contributing to this interaction. Overall, this thesis provides insight into the airway mechanics, intestinal disease, immune system, bone disease and the intestinal microbiome in cystic fibrosis. We also investigated the interactions between these disease components, showing a connection between the CF intestinal microbiome and the airway mechanics." --

Evolution of Animal Microbial Communities in Response to Environmental Stress

Antibiofilm Agents

This book provides a survey of recent advances in the development of antibiofilm agents for clinical and environmental applications. The fact that microbes exist in structured communities called biofilms has slowly become accepted within the medical community. We now know that over 80% of all infectious diseases are biofilm-related; however, significant challenges still lie in our ability to diagnose and treat these extremely recalcitrant infections. Written by experts from around the globe, this book offers a valuable resource for medical professionals seeking to treat biofilm-related disease, academic and industry researchers interested in drug discovery and instructors who teach courses on microbial pathogenesis and medical microbiology.