Microbiome networks and change-point analysis reveal key community changes associated with cystic fibrosis pulmonary exacerbations

Over 90% of cystic fibrosis (CF) patients die due to chronic lung infections leading to respiratory failure. The decline in CF lung function is greatly accelerated by intermittent and progressively severe acute pulmonary exacerbations (PEs). Despite their clinical impact, surprisingly few microbiological signals associated with PEs have been identified. Here we introduce an unsupervised, systems-oriented approach to identify key members of the microbiota. We used two CF sputum microbiome data sets that were longitudinally collected through periods spanning baseline health and PEs. Key taxa were defined based on three strategies: overall relative abundance, prevalence, and co-occurrence network interconnectedness. We measured the association between changes in the abundance of the key taxa and changes in patient clinical status over time via change-point detection, and found that taxa with the highest level of network interconnectedness tracked changes in patient health significantly better than taxa with the highest abundance or prevalence. We also cross-sectionally stratified all samples into the clinical states and identified key taxa associated with each state. We found that network interconnectedness most strongly delineated the taxa among clinical states, and that anaerobic bacteria were over-represented during PEs. Many of these anaerobes are oropharyngeal bacteria that have been previously isolated from the respiratory tract, and/or have been studied for their role in CF. The observed shift in community structure, and the association of anaerobic taxa and PEs lends further support to the growing consensus that anoxic conditions and the subsequent growth of anaerobic microbes are important predictors of PEs. Cystic Fibrosis: Oxygen, microbes and exacerbation Episodes of significant worsening of cystic fibrosis symptoms, known as pulmonary exacerbations (PEs), are associated with oxygen-deficient (anoxic) conditions and increased activity of ‘anaerobic’ bacteria, which thrive in the absence of oxygen. Researchers in Canada, led by David Guttman at the University of Toronto, compared genetic data on microbial populations in sputum samples collected during PEs and at times of better health. The study revealed a strong correlation between the activity and interactions among anaerobic bacteria and the onset of PEs. Investigating the significance of these changes in the lung environment and its microbial populations may help design treatment strategies to