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NPJ Biofilms Microbiomes. 2019 Jan 21;5:4. doi: 10.1038/s41522-018-0077-y. eCollection 2019.

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

Author information

1
1Department of Cell and Systems Biology, University of Toronto, Toronto, ON Canada.
2
2Department of Biochemistry, University of Toronto, Toronto, ON Canada.
3
3Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, ON Canada.
4
4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada.
5
5Latner Thoracic Surgery Laboratories, University Health Network, University of Toronto, Toronto, ON Canada.
6
6Adult Cystic Fibrosis Clinic, St. Michael's Hospital, Toronto, ON Canada.
7
7Department of Pediatric Laboratory Medicine, Microbiology, The Hospital for Sick Children, Toronto, ON Canada.
8
8Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada.
9
9Division of Infectious Diseases, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON Canada.
10
10Department of Pathology, University Health Network, University of Toronto, Toronto, ON Canada.

Abstract

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.

Conflict of interest statement

The authors declare no competing interests.

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