Abstract
The major therapeutic strategy used to treat exacerbated cystic fibrosis (CF) is antibiotic treatment. As this approach easily generates antibiotic-resistant strains of opportunistic bacteria, optimized antibiotic therapies are required to effectively control chronic and recurrent bacterial infections in CF patients. A promising future for the proper use of antibiotics is the management of lung microbiota. However, the impact of antibiotic treatments on CF microbiota and vice versa is not fully understood. This study analyzed 718 sputum samples from 18 previous studies to identify differences between CF and uninfected lung microbiota and to evaluate the effects of antibiotic treatments on exacerbated CF microbiota. A reference-based OTU (operational taxonomic unit) picking method was used to combine analyses of data generated using different protocols and platforms. Findings show that CF microbiota had greater richness and lower diversity in the community structure than uninfected control (NIC) microbiota. Specifically, CF microbiota showed higher levels of opportunistic bacteria and dramatically lower levels of commensal bacteria. Antibiotic treatment affected exacerbated CF microbiota notably but only transiently during the treatment period. Limited decrease of the dominant opportunistic bacteria and a dramatic decrease of commensal bacteria were observed during the antibiotic treatment for CF exacerbation. Simultaneously, low abundance opportunistic bacteria were thriving after the antibiotic treatment. The inefficiency of the current antibiotic treatment against major opportunistic bacteria and the detrimental effects on commensal bacteria indicate that the current empiric antibiotic treatment on CF exacerbation should be reevaluated and optimized.
Highlights
Cystic fibrosis (CF), as an inherited disease of the secretory glands, is caused by defective mutations of the CF transmembrane conductance regulator (CFTR) gene [1,2,3]
This study analyzed a large cohort of lung microbiota samples from CF patients and healthy individuals from cross-sectional studies to compare the community structures and to evaluate the impact of antibiotic treatment on lung microbiota
Overall our results demonstrate that antibiotic treatments for CF exacerbation have limited effects on opportunistic bacteria but dramatic effects on commensal bacteria
Summary
Cystic fibrosis (CF), as an inherited disease of the secretory glands, is caused by defective mutations of the CF transmembrane conductance regulator (CFTR) gene [1,2,3]. Thickened mucus secretions resulting from the defective CFTR enable the development and persistence of pulmonary bacterial infections [4, 5]. These chronic pulmonary infections, which are mainly. As a result of chronic polymicrobial infection and inflammation, CF is a devastating life-threatening disease with the majority of mortalities due to respiratory failure [6, 7]. Over the course of CF lung disease two categories have been identified according to disease severity: exacerbated and clinically stable. A clinically stable condition is the stationary phase before or after pulmonary exacerbation
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