Parkins, Michael D.Storey, Douglas G.Heirali, Alya2020-01-212020-01-212020-01-20Heirali, A. (2020). Exploring the Effects of Inhaled Antibiotics on the Cystic Fibrosis Lung Microbiome and Pseudomonas aeruginosa Population Diversity and their Clinical Implications (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/111532The CF lung microbiome is composed of a diverse group of microorganisms. Where the constituents of the microbiome originate from remains poorly understood. The work presented herein shows that the home environment may serve as a reservoir for infection in patients with CF. Researchers have demonstrated that the CF lung microbial communities are dynamic and complex. As patients age and disease progression occurs the diversity of organisms colonizing the lower airways generally decreases and patients become dominated by organisms such as Pseudomonas aeruginosa. Several studies have attempted to increase our understanding of the shifts in the microbial communities prior to pulmonary exacerbations. However, there is a tremendous knowledge gap on how the microbiome changes through chronic suppressive inhaled antibiotics used by the majority of CF patients in Canada. Accordingly, we sought to investigate how inhaled aztreonam and tobramycin affect the CF lung microbiome and whether the microbiome can be used as a tool to predict patient response. We showed that the lung microbiome is relatively fixed in adults with CF despite potent inhaled antibacterial therapy. The relative abundance of Staphylococcus was associated with response in all three studies assessing the effects of inhaled antibiotics on the lung microbiome. Specifically, a higher abundance of Staphylococcus at baseline was associated with non-response to inhaled aztreonam and response to inhaled tobramycin – mirroring expected antibacterial activity and suggesting a potential biomarker for treatment response. Keywords: lung microbiome, cystic fibrosis, inhaled antibiotics, Staphylococcus, P. aeruginosa, biomarkerengUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.BioinformaticsMicrobiologyBiology--MolecularBiophysics--Medicaldoctoral thesis10.11575/PRISM/37484