The Respiratory Microbiome in Cystic Fibrosis: Compartment Patterns and Clinical Relationships in Early Stage Disease

Abstract

We compared the bacterial microbiomes lodged in the bronchial tree, oropharynx and nose of patients with early stage cystic fibrosis (CF) not using chronic antibiotics, determining their relationships with lung function and exacerbation frequency. CF patients were enrolled in a cohort study during stability and were checked regularly over the following 9 months. Upper respiratory samples (sputum [S], oropharyngeal swab [OP] and nasal washing [N]) were collected at the first visit and every 3 months. 16S rRNA gene amplification and sequencing was performed and analyzed with QIIME. Seventeen CF patients were enrolled (16.6 SD 9.6 years). Alpha-diversity of bacterial communities between samples was significantly higher in S than in OP (Shannon index median 4.6 [IQR: 4.1–4.9] vs. 3.7 [IQR: 3-1-4.1], p = 0.003/Chao 1 richness estimator median 97.75 [IQR: 85.1–110.9] vs. 43.9 [IQR: 31.7–59.9], p = 0.003) and beta-diversity analysis also showed significant differences in the microbial composition of both respiratory compartments (Adonis test of Bray Curtis dissimilarity matrix, p = 0.001). Dominant taxa were found at baseline in five patients (29.4%), who showed lower forced expiratory volume in the first second (FEV1%, mean 74.8 [SD 19] vs. 97.2 [SD 17.8], p = 0.035, Student t test). The Staphylococcus genus had low RAs in most samples (median 0.26% [IQR 0.01–0.69%]), but patients with RA > 0.26% of Staphylococcus in bronchial secretions suffered more exacerbations during follow-up (median 2 [IQR 1–2.25] vs. 0 [0–1], p = 0.026. Mann–Whitney U test), due to S. aureus in more than a half of the cases, microorganism that often persists as bronchial colonized in these patients (9/10 [90%] vs. 2/7 [28.6%], p = 0.034, Fisher’s exact test). In conclusion, the bronchial microbiome had significantly higher diversity than the microbial flora lodged in the oropharynx in early stage CF. Although the RA of the Staphylococcus genus was low in bronchial secretions and did not reach a dominance pattern, slight overrepresentations of this genus was associated with higher exacerbation frequencies in these patients.

Phenotypic and Genomic Variability of Serial Peri-Lung Transplantation Pseudomonas aeruginosa Isolates From Cystic Fibrosis Patients

“…Also, the microbes have an ability to integrate exogenous DNA to withstand the selective pressure of antibiotics. Thus, in order to understand these dynamics, there have been various efforts to understand the correlation of genotype and phenotype (e.g., response to antibiotics) by several researchers ( Mena et al, 2008 ; Hazan et al, 2014 ; Macia et al, 2014 ; Sousa and Pereira, 2014 ; Kos et al, 2015 ; Jaillard et al, 2017 ; Lozano et al, 2018 ; Garcia-Nuñez et al,2020 ). Furthermore, the MLST profiles derived from two different tools-PubMLST and EPISEQ and the phenotypic antibiotic susceptibility profiles shows disparity.…”

The respiratory microbiome associated with chronic obstructive pulmonary disease comorbidity in non‐small cell lung cancer

“…Moreover, an increasing number of studies reveal an association between pulmonary microbiota (or dysbiosis) and lung diseases. These diseases include chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, and idiopathic pulmonary fibrosis (IPF) 4–7 …”

“…These diseases include chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, and idiopathic pulmonary fibrosis (IPF). [4][5][6][7] Furthermore, some microbiomes have been linked to cancer. For example, infection with Helicobacter pylori (H. pylori), Fusobacterium nucleatum, human papilloma virus, and Escherichia coli can lead to various types of cancer.…”

“…These diseases include chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, and idiopathic pulmonary fibrosis (IPF). 4 , 5 , 6 , 7 …”

The Airway Microbiome-IL-17 Axis: a Critical Regulator of Chronic Inflammatory Disease

“…Conversely, reduced bacterial diversity and increased dominance of certain species, particularly S. aureus and H. influenzae, correlates with antibiotic use, age and heightened inflammation [7,129,132,133]. From late childhood onwards Mycobacterium abscessus, Burkholderia cenocepacia and Pseudomonas aeruginosa begin to dominate and are strongly associated with disease progression [134][135][136][137][138][139]. Nevertheless, recent culture-independent studies have found that both the early stage and adult CF lung is more polymicrobial than previously thought [140,141].…”