Cystic fibrosis respiratory microbiota: unraveling complexity to inform clinical practice

ABSTRACT

Introduction: Cystic fibrosis (CF) lung disease is characterized by chronic cycles of pulmonary infection, inflammation, and mucus obstruction, beginning early in life, and eventually leading to progressive lung damage and early mortality. During the past ~15 years, culture-independent analyses of CF respiratory samples have identified diverse bacterial communities in CF airways, and relationships between respiratory microbiota and clinical outcomes.

Areas covered: This paper reviews recent advances in our understanding of the relationships between respiratory microbiota and CF lung disease. The paper focuses on measures of airway bacterial community diversity and estimates of the relative abundance of anaerobic species. Finally, this paper will review the opportunities for advancing patient care suggested by these studies and highlight some of the ongoing challenges and unmet needs in translating this knowledge into clinical practice.

Expert commentary: Culture-independent analyses of respiratory microbiota have suggested new strategies for advancing CF care, but have also highlighted challenges in understanding the complexity of CF respiratory infections. Development of more sophisticated models and analytic approaches to better account for this complexity are needed to elucidate mechanistic links between CF respiratory microbiota and clinical outcomes, and to ultimately translate this knowledge into better patient care.

KEYWORDS:

• Cystic fibrosis
• microbiome
• metabolomics
• anaerobes
• exacerbation

Key issues

• Initial culture-independent studies of CF respiratory microbiota identified diverse bacterial communities, including genera not routinely identified by clinical laboratory culture.

• Multiple clinical variables have bearing on respiratory microbiota: clinical state, lung disease stage, disease aggressiveness, antibiotic use, and inter-subject variability.

• Over time, diverse respiratory bacterial communities containing anaerobes typically found in oral microbiota are replaced by less diverse communities dominated by typical CF pathogens.

• Less-diverse bacterial communities have been associated with poorer clinical outcomes, including pulmonary exacerbations and lung function decline, starting in childhood.

• Universal changes in respiratory microbiota associated with pulmonary exacerbation have not been identified, but common motifs of within-subject changes have been suggested, including changes in the dominant pathogen and alterations in baseline community stability.

• Relationships between the presence, relative abundance, and metabolic activities of anaerobic genera and pulmonary exacerbations have been identified.

• Multiple features of respiratory microbiota have been identified that likely influence efficacy of antibiotic therapy, including bacterial interactions, regional lung disease heterogeneity, and the chemical composition of CF sputum.

• Further development of more sophisticated models and analytic approaches to links between CF respiratory microbiota and lung disease are needed.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Cystic Fibrosis Foundation [grant number CAVERL17A0], [grant number LIPUMA15P0] and the National Institutes of Health, National Heart, Lung, and Blood Institute [grant number 1 R01 HL 136647-01], [grant number K23HL136934].