Article Text
Abstract
Introduction Pseudomonas aeruginosa pulmonary infections are the primary cause of morbi-mortality in patients with cystic fibrosis (CF). In this cohort study, the objective was to identify candidate biomarkers of P. aeruginosa infection within the airway microbiota.
Methods A 3-year prospective multicentre study (PYOMUCO study) was conducted in Western France and included patients initially P. aeruginosa free for at least 1 year. A 16S-targeted metagenomics approach was applied on iterative sputum samples of a first set of patients (n=33). The composition of airway microbiota was compared according to their P. aeruginosa status at the end of the follow-up (colonised vs non-colonised), and biomarkers associated with P. aeruginosa were screened. In a second step, the distribution of a candidate biomarker according to the two groups of patients was verified by qPCR on a second set of patients (n=52) coming from the same cohort and its load quantified throughout the follow-up.
Results Porphyromonas (mainly P. catoniae) was found to be an enriched phylotype in patients uninfected by P. aeruginosa (p<0.001). This result was confirmed by quantitative PCR. Conversely, in patients who became P. aeruginosa-positive, P. catoniae significantly decreased before P. aeruginosa acquisition (p=0.014).
Discussion Further studies on replication cohorts are needed to validate this potential predictive biomarker, which may be relevant for the follow-up in the early years of patients with CF. The identification of infection candidate biomarkers may offer new strategies for CF precision medicine.
- cystic fibrosis
- microbiota
- biomarkers
- pseudomonas aeruginosa
- porphyromonas
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Footnotes
Contributors GH-A and JM conceived the study. SG, C-AG and MK performed DNA extraction, qPCR and pyrosequencing. MK, JM, PL and GB performed pyrosequencing data and statistical analysis. MK, C-AG, M-SF and SG performed multiplex PCR. GH-A, RLB, CF and GR contributed to data collection. JM, PL, SV and SM contributed to design. MK, GH-A, JM and PL wrote the manuscript. All authors participated in data analysis and editing the manuscript for final approval. GH-A and JM take overall responsibility for the content of the manuscript.
Funding This work was supported by a grant from the French Cystic Fibrosis Associations ‘Vaincre la Mucoviscidose’ and ‘Grégory Lemarchal’ (contract no. RC20170501971).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval Two review boards, the local Comité de Protection des Personnes VI-Ouest and the institutional review board of the Brest University Hospital Centre, approved the protocol.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.
Author note The study was presented in part at the 41th European Cystic Fibrosis Conference, 8–11 June 2018, in Belgrade, Serbia. A European patent has been registered (no. EP17306297).