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 1year. 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 prevision medicine.