Lower Respiratory Tract Microbiota Research Articles

Distinct lower respiratory tract microbiota profiles linked to airway mucus hypersecretion in children with Mycoplasma pneumoniae pneumonia.

Airway mucus hypersecretion (AMH) can occur in children with acute respiratory diseases, but its underlying mechanisms and relationship with the lower respiratory tract microbiota (LRTM) are not yet fully understood. This study investigates the characteristics of LRTM in children with Mycoplasma pneumoniae pneumonia (MPP) and its impact on AMH. We collected bronchoalveolar lavage fluid and related clinical indicators from 202 children with MPP. 16S rRNA gene amplicon sequencing was used for detection and identification. Microbial diversity and characteristic genera were compared, and their abundance was analyzed for correlations with clinical factors. As the disease course (days from onset to bronchoscopy, grouped into T1, T2, T3) extended, α-diversity of the LRTM gradually increased, particularly in the T3 hypersecretion group. Moreover, significant differences were observed in the incidence of AMH, co-infection rates, peripheral white blood cell (WBC) count, and C-reactive protein levels. In AMH, Mycoplasmoides and Veillonella abundance and peripheral neutrophils were risk factors for increased secretions. In addition, in the T3 co-infection group, Streptococcus and Prevotella increased, replacing Stenotrophomonas as the dominant genus, possibly due to β-lactam antibiotic use. Prevotella abundance was strongly correlated with WBC. The composition and structure of LRTM in children with MPP played a crucial role in AMH and disease progression.

Lower respiratory tract microbiota in patients with clinically suspected nontuberculous mycobacterial pulmonary disease according to the presence of gastroesophageal reflux.

Although gastroesophageal reflux has been recognized as one of the risk factors of nontuberculous mycobacterial pulmonary disease (NTM-PD) progression, the effect of reflux on the lower respiratory tract microbiota has not been studied in detail. We investigated the composition of the lower respiratory tract microbiota in patients with clinically suspected NTM-PD, comparing them based on the presence of reflux. Forty-seven patients suspected of having NTM-PD were enrolled and assigned according to presence of reflux (n = 22) and non- reflux (n = 25). We performed a pepsin ELISA assay to identify the presence of reflux and 16S ribosomal RNA gene amplicon sequencing to evaluate the microbiota in bronchoalveolar lavage fluid. There were no significant differences in the diversity or composition of the lower respiratory microbiota between the NTM-PD and non-NTM-PD groups. Bacterial richness was observed in the non-reflux group than in the reflux group [P = 0.03] and a cluster in the reflux group was observed. The reflux group showed a predominance for Pseudomonas aeruginosa or Staphylococcus aureus among the NTM-PD group and for P. aeruginosa, Haemophilus influenzae, Klebsiella pneumoniae, or Eikenella species among the non-NTM-PD group. The non-reflux groups presented diverse patterns. A linear discriminant analysis and volcano plot demonstrated that P. aeruginosa, H. haemolyticus, Selenomonas artemidis, and Dolosigranulum pigrum were specifically associated with the NTM-PD reflux group, while P. aeruginosa was specifically associated with the non-NTM-PD reflux group. These observations confirm that the lower respiratory microbiota is consistently altered by reflux but not in NTM-PD.

Microbiome features in bronchoalveolar lavage fluid of patients with idiopathic inflammatory myopathy-related interstitial lung disease.

Interstitial lung disease (ILD) is a common complication of idiopathic inflammatory myopathy (IIM), which is one of the connective tissue diseases (CTD). It can lead to poor prognosis and increased mortality. However, the distribution and role of the lower respiratory tract (LRT) microbiome in patients with IIM-ILD remains unclear. This study aimed to investigate the microbial diversity and community differences in bronchoalveolar lavage fluid (BALF) in patients with IIM-ILD. From 28 June 2021 to 26 December 2023, 51 individual BALF samples were enrolled, consisting of 20 patients with IIM-ILD, 16 patients with other CTD-ILD (including 8 patients with SLE and 8 with RA) and 15 patients with CAP. The structure and function of microbiota in BALF were identified by metagenomic next-generation sequencing (mNGS). The community evenness of LRT microbiota within the IIM-ILD group was marginally lower compared to the other CTD-ILD and CAP groups. Nonetheless, there were no noticeable differences. The species community structure was similar among the three groups, based on the Bray-Curtis distance between the samples. At the level of genus, the IIM-ILD group displayed a considerably higher abundance of Pseudomonas and Corynebacterium in comparison to the CAP group (p < 0.01, p < 0.05). At the species level, we found that the relative abundance of Pseudomonas aeruginosa increased significantly in the IIM-ILD group compared to the CAP group (p < 0.05). Additionally, the relative abundance of Prevotella pallens was significantly higher in other CTD-ILD groups compared to that in the IIM-ILD group (p < 0.05). Of all the clinical indicators examined in the correlation analysis, ferritin level demonstrated the strongest association with LRT flora, followed by Serum interleukin-6 level (p < 0.05). Our research has identified particular LRT microorganisms that were found to be altered in the IIM-ILD group and were significantly associated with immune function and inflammatory markers in patients. The lower respiratory tract microbiota has potential in the diagnosis and treatment of IIM-ILD.

Altered Respiratory Microbiomes, Plasma Metabolites, and Immune Responses in Influenza A Virus and Methicillin-Resistant Staphylococcus aureus Coinfection.

Influenza A virus (IAV)-methicillin-resistant Staphylococcus aureus (MRSA) coinfection causes severe respiratory infections. The host microbiome plays an important role in respiratory tract infections. However, the relationships among the immune responses, metabolic characteristics, and respiratory microbial characteristics of IAV-MRSA coinfection have not been fully studied. We used specific-pathogen-free (SPF) C57BL/6N mice infected with IAV and MRSA to build a nonlethal model of IAV-MRSA coinfection and characterized the upper respiratory tract (URT) and lower respiratory tract (LRT) microbiomes at 4 and 13 days postinfection by full-length 16S rRNA gene sequencing. Immune response and plasma metabolism profile analyses were performed at 4 days postinfection by flow cytometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relationships among the LRT microbiota, the immune response, and the plasma metabolism profile were analyzed by Spearman's correlation analysis. IAV-MRSA coinfection showed significant weight loss and lung injury and significantly increased loads of IAV and MRSA in bronchoalveolar lavage fluid (BALF). Microbiome data showed that coinfection significantly increased the relative abundances of Enterococcus faecalis, Enterobacter hormaechei, Citrobacter freundii, and Klebsiella pneumoniae and decreased the relative abundances of Lactobacillus reuteri and Lactobacillus murinus. The percentages of CD4+/CD8+ T cells and B cells in the spleen; the levels of interleukin-9 (IL-9), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-6, and IL-8 in the lung; and the level of mevalonolactone in plasma were increased in IAV-MRSA-coinfected mice. L. murinus was positively correlated with lung macrophages and natural killer (NK) cells, negatively correlated with spleen B cells and CD4+/CD8+ T cells, and correlated with multiple plasma metabolites. Future research is needed to clarify whether L. murinus mediates or alters the severity of IAV-MRSA coinfection. IMPORTANCE The respiratory microbiome plays an important role in respiratory tract infections. In this study, we characterized the URT and LRT microbiota, the host immune response, and plasma metabolic profiles during IAV-MRSA coinfection and evaluated their correlations. We observed that IAV-MRSA coinfection induced severe lung injury and dysregulated host immunity and plasma metabolic profiles, as evidenced by the aggravation of lung pathological damage, the reduction of innate immune cells, the strong adaptation of the immune response, and the upregulation of mevalonolactone in plasma. L. murinus was strongly correlated with immune cells and plasma metabolites. Our findings contribute to a better understanding of the role of the host microbiome in respiratory tract infections and identified a key bacterial species, L. murinus, that may provide important references for the development of probiotic therapies.

Characteristics of lower respiratory tract microbiota in the patients with post-hematopoietic stem cell transplantation pneumonia.

BackgroundPneumonia is a leading cause of non-relapse mortality after hematopoietic stem cell transplantation (HSCT), and the lower respiratory tract (LRT) microbiome has been proven to be associated with various respiratory diseases. However, little is known about the characteristics of the LRT microbiome in patients with post-HSCT compared to healthy controls (HC) and community-acquired pneumonia (CAP).MethodsBronchoalveolar lavage samples from 55 patients with post-HSCT pneumonia, 44 patients with CAP, and 30 healthy volunteers were used to detect microbiota using 16S rRNA gene sequencing.ResultsThe diversity of the LRT microbiome significantly decreased in patients with post-HSCT pneumonia, and the overall community was different from the CAP and HC groups. At the phylum level, post-HSCT pneumonia samples had a high abundance of Actinobacteria and a relatively low abundance of Bacteroidetes. The same is true for non-survivors compared with survivors in patients with post-HSCT pneumonia. At the genus level, the abundances of Pseudomonas, Acinetobacter, Burkholderia, and Mycobacterium were prominent in the pneumonia group after HSCT. On the other hand, gut-associated bacteria, Enterococcus were more abundant in the non-survivors. Some pathways concerning amino acid and lipid metabolism were predicted to be altered in patients with post-HSCT pneumonia.ConclusionsOur results reveal that the LRT microbiome in patients with post-HSCT pneumonia differs from CAP patients and healthy controls, which could be associated with the outcome. The LRT microbiota could be a target for intervention during post-HSCT pneumonia.

Современные аспекты изучения респираторной микробиоты и ее роль в развитии инфекций нижних дыхательных путей

Novel molecular methods allowed us to reassess microbial diversity of the respiratory microbiota and its role for the host. A new look at the respiratory microbiota as a potential pathogenic agent opens up new perspectives for understanding the etiopathogenesis of infectious diseases. The microbiota of the lower respiratory tract, which includes various bacteria, viruses, bacteriophages, and fungi, is particularly interesting. A number of studies analyzed upper and lower respiratory tract microbiota in patients with pneumonia and found that it was often challenging to identify a single causative agent of pneumonia from the standpoint of the concept that ‘microbiota is a pathogen’. The different etiology of pneumonia is likely to be associated with specific patterns of respiratory dysbiosis. Patients with pneumonia tend to have lower species diversity and greater bacterial microbiota density. Furthermore, there is a positive correlation between bacterial density of the rhinopharyngeal microbiota and severity of pneumonia. A number of microbial profiles were found to be associated with pneumonia, including those with a high relative abundance of lactobacilli and predominance of Rothia and Streptococcus pneumoniae (pseudopneumoniae). However, no protective commensal microbiota profile has been yet found. Treatment of respiratory dysbiosis with inhaled and nasal probiotics appears promising, but it requires further studies. Key words: lungs, microbiota, pneumonia, sequencing, 16S ribosomal RNA

Respiratory Tract Dysbiosis Is Associated with Worse Outcomes in Mechanically Ventilated Patients.

Rationale: Host inflammatory responses have been strongly associated with adverse outcomes in critically ill patients, but the biologic underpinnings of such heterogeneous responses have not been defined.Objectives: We examined whether respiratory tract microbiome profiles are associated with host inflammation and clinical outcomes of acute respiratory failure.Methods: We collected oral swabs, endotracheal aspirates (ETAs), and plasma samples from mechanically ventilated patients. We performed 16S ribosomal RNA gene sequencing to characterize upper and lower respiratory tract microbiota and classified patients into host-response subphenotypes on the basis of clinical variables and plasma biomarkers of innate immunity and inflammation. We derived diversity metrics and composition clusters with Dirichlet multinomial models and examined our data for associations with subphenotypes and clinical outcomes.Measurements and Main Results: Oral and ETA microbial communities from 301 mechanically ventilated subjects had substantial heterogeneity in α and β diversity. Dirichlet multinomial models revealed a cluster with low α diversity and enrichment for pathogens (e.g., high Staphylococcus or Pseudomonadaceae relative abundance) in 35% of ETA samples, associated with a hyperinflammatory subphenotype, worse 30-day survival, and longer time to liberation from mechanical ventilation (adjusted P < 0.05), compared with patients with higher α diversity and relative abundance of typical oral microbiota. Patients with evidence of dysbiosis (low α diversity and low relative abundance of "protective" oral-origin commensal bacteria) in both oral and ETA samples (17%, combined dysbiosis) had significantly worse 30-day survival and longer time to liberation from mechanical ventilation than patients without dysbiosis (55%; adjusted P < 0.05).Conclusions: Respiratory tract dysbiosis may represent an important, modifiable contributor to patient-level heterogeneity in systemic inflammatory responses and clinical outcomes.

Lower respiratory tract microbial composition was diversified in Pseudomonas aeruginosa ventilator-associated pneumonia patients

BackgroundProbiotics could prevent Pseudomonas aeruginosa colonization in lower respiratory tract (LRT) and reduced P. aeruginosa ventilator-associated pneumonia (VAP) rate. Recent studies also suggested that probiotics could improve lung inflammation in mice infected with P. aeruginosa. It seems that microbiota regulation may be a potential therapy for P. aeruginosa VAP patients. However, we know less about the LRT microbial composition and its correlation with prognosis in P. aeruginosa VAP patients. This study aimed to characterize LRT microbiota in P. aeruginosa VAP patients and explore the relationship between microbiota and patient prognosis.MethodsDeep endotracheal secretions were sampled from subjects via intubation. Communities were identified by 16S ribosomal RNA gene sequencing. The relationship between microbiota and the prognosis of P. aeruginosa VAP patients were evaluated. Clinical pulmonary infection score and the survival of intensive care unit were both the indicators of patient prognosis.ResultsIn this study, the LRT microbial composition of P. aeruginosa VAP patients was significantly different from non-infected intubation patients, and showed significant individual differences, forming two clusters. According to the predominant phylum of each cluster, these two clusters were named Pro cluster and Fir-Bac cluster respectively. Patients from Pro cluster were dominated by Proteobacteria (adj.P < 0.001), while those from Fir-Bac cluster were dominated by Firmicutes, and Bacteroidetes (both adj.P < 0.001). These two varied clusters (Pro and Fir-Bac cluster) were associated with the patients’ primary disease (χ2-test, P < 0.0001). The primary disease of the Pro cluster mainly included gastrointestinal disease (63%), and the Fir-Bac cluster was predominantly respiratory disease (89%). During the two-week dynamic observation period, despite the use of antibiotics, the dominant genera and Shannon diversity of the LRT microbiota did not change significantly in patients with P. aeruginosa VAP. In prognostic analysis, we found a significant negative correlation between Lactobacillus and clinical pulmonary infection score on the day of diagnosis (P = 0.014); but we found no significant difference of microbial composition between survivors and non-survivors.ConclusionsLRT microbial composition was diversified among P. aeruginosa VAP patients, forming two clusters which were associated with the primary diseases of the patients.

Relation between lower respiratory tract microbiota and type of immune response against tuberculosis

In this study, the interaction between the microbiota of the lower respiratory tract and the type of immune response against Mycobacterium tuberculosis were studied. Bronchoalveolar lavage (BAL) samples of 10 tuberculosis (TB) patients and 5 cases suspected of lung cancer as control were obtained. Clinical symptoms were recorded for the TB patients. Serial dilutions of samples were prepared and cultured on a selective medium in order to count Streptococcus spp., Neisseria spp., Haemophilus spp. and Veillonella in the lung. To determine the type of immune response of Th1/Th2, Real Time-PCR method was used. The prevalence of Streptococcus spp. in the lungs of patients with TB increased when compared with the control group and the Th1-response in this group may be influenced by Neisseria and Haemophilus. However, reducing the number of Streptococcus and Neisseria can be involved in the development of Th1-response in the control group. Prevalence of Neisseria and Veillonella of the lung microbiota in this group may be associated with fever. The chest x-ray influenced both Th1 and Th2-responses in the lung, but only Th1-response was involved in reducing the weight of patients. The relationship between each of the clinical symptoms with immune response and with each genus of microbiota were reviewed separately, and these data are the new information on TB disease and can be the beginning of the study on the impact of genus, different species and strains of microbiota on the clinical signs of disease.

Characterization of the upper and lower respiratory tract microbiota in Piedmontese calves

BackgroundThe microbiota of the bovine upper respiratory tract has been recently characterized, but no data for the lower respiratory tract are available. A major health problem in bovine medicine is infectious bronchopneumonia, the most common respiratory syndrome affecting cattle. With this study, we used 16S rRNA gene sequencing to characterize and compare the microbial community composition of the upper and lower respiratory tracts in calves.ResultsThe microbiota of the upper (nasal swab [NS]) and the lower (trans-tracheal aspiration [TTA]) respiratory tracts of 19 post-weaned Piedmontese calves with (8/19) and without (11/19) clinical signs of respiratory disease, coming from six different farms, was characterized by 16S rRNA gene metabarcoding. A total of 29 phyla (29 in NS, 21 in TTA) and 305 genera (289 in NS, 182 in TTA) were identified. Mycoplasma (60.8%) was the most abundant genus identified in both the NS (27.3%) and TTA (76.7%) samples, followed by Moraxella (16.6%) in the NS and Pasteurella (7.3%) in the TTA samples. Pasteurella multocida (7.3% of total operational taxonomic units [OTUs]) was the most abundant species in the TTA and Psychrobacter sanguinis (1.1% of total OTUs) in the NS samples. Statistically significant differences between the NS and the TTA samples were found for both alpha (Shannon index, observed species, Chao1 index, and Simpson index; P = 0.001) and beta (Adonis; P = 0.001) diversity. Comparison of the NS and TTA samples by farm origin and clinical signs revealed no statistical difference (P > 0.05), except for farm origin for the NS samples when compared by the unweighted UniFrac metric (P = 0.05).ConclusionsUsing 16S rRNA gene sequencing, we characterized the microbiota of the upper and lower respiratory tracts of calves, both healthy individuals and those with clinical signs of respiratory disease. Our results suggest that environmental factors may influence the composition of the upper airway microbiota in cattle. While the two microbial communities (upper and lower airways) differed in microbial composition, they shared several OTUs, suggesting that the lung microbiota may be a self-sustaining, more homogeneous ecosystem, influenced by the upper respiratory tract microbiota.

Relationship between nasopharyngeal and bronchoalveolar microbial communities in clinically healthy feedlot cattle

BackgroundThe importance of upper airway structure in the susceptibility of the lower respiratory tract to colonization with potential pathogens is well established. With the advent of rapid, high throughput, next generation sequencing, there is a growing appreciation of the importance of commensal microbial populations in maintaining mucosal health, and a realization that bacteria colonize anatomical locations that were previously considered to be sterile. While upper respiratory tract microbial populations have been described, there are currently no published studies describing the normal microbial populations of the bovine lower respiratory tract. Consequently, we have little understanding of the relationship between upper and lower respiratory tract microbiota in healthy cattle. The primary objective of our study was to characterize the composition, structure and relationship of the lower and upper respiratory microbial communities in clinically healthy feedlot cattle. Nasopharyngeal swabs (NPS), and bronchoalveolar lavage (BAL) fluid, were collected from clinically healthy feedlot calves (n = 8). Genomic DNA from each sample was extracted, and the V3-V4 hypervariable region of the bacterial 16S rRNA gene was amplified and sequenced using Illumina Miseq platform.ResultsAcross all samples, the most predominant phyla were Proteobacteria, Actinobacteria and Firmicutes. The most common genera were Rathayibacter, Mycoplasma, Bibersteinia and Corynebacterium. The microbial community structure was distinct between these two biogeographical sites. Most of the bacterial genera identified in the BAL samples were also present in the NPS, but biogeographical-specific genera were enriched in both the NPS (Rathayibacter) and BAL (Bibersteinia) samples. There were strong associations between the presence of certain taxa at each specific location, and strong correlations between the presence of specific taxa in both the NPS and BAL samples.ConclusionsThe correlation between the presence of specific taxa in both the NPS and BAL samples, supports the notion of a mutualistic interrelationship between these microbial communities. Future studies, in large cohorts of animals, are needed to determine the role and clinical importance of the relationships of respiratory tract microbial communities with health, productivity, and susceptibility to the development of respiratory disease, in growing cattle.

The microbiome in respiratory medicine: current challenges and future perspectives.

The healthy lung has previously been considered to be a sterile organ because standard microbiological culture techniques consistently yield negative results. However, culture-independent techniques report that large numbers of microorganisms coexist in the lung. There are many unknown aspects in the field, but available reports show that the lower respiratory tract microbiota: 1) is similar in healthy subjects to the oropharyngeal microbiota and dominated by members of the Firmicutes, Bacteroidetes and Proteobacteria phyla; 2) shows changes in smokers and well-defined differences in chronic respiratory diseases, although the temporal and spatial kinetics of these changes are only partially known; and 3) shows relatively abundant non-cultivable bacteria in chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis and bronchiectasis, with specific patterns for each disease. In all of these diseases, a loss of diversity, paralleled by an over-representation of Proteobacteria (dysbiosis), has been related to disease severity and exacerbations. However, it is unknown whether dysbiosis is a cause or a consequence of the damage to bronchoalveolar surfaces.Finally, little is known about bacterial functionality and the interactions between viruses, fungi and bacteria. It is expected that future research in bacterial gene expressions, metagenomics longitudinal analysis and host-microbiome animal models will help to move towards targeted microbiome interventions in respiratory diseases.

The Nasal Microbiome in Asthma

Lower respiratory tract microbiota have been associated with asthma development and severity. We hypothesized that the nasal microbiome differs between healthy and asthmatic individuals. Nasal swabs were obtained from 73 subjects recruited from the Mount Sinai Health System (New York, NY), including 22 with exacerbated asthma, 31 with stable asthma, and 20 non-asthmatic controls. The nasal microbiome was profiled by 16S rRNA sequencing and analyses were performed using QIIME (Quantitative Insights into Microbial Ecology), PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), and STAMP (Statistical Analysis of Metagenomic Profiles). Mean age of the cohort was 35.7 years (standard deviation 15.9) with 66% female. Seventy five percent of subjects with exacerbated asthma, 45% of subjects with stable asthma, and 0% of controls had ≥1 hospitalization for asthma in the past year. Nasal bacterial compositions between the classes were significantly different (PERMANOVA η2=5%; P=2.2x10-2). Relative to controls, the nasal microbiota of subjects with asthma were enriched with Bacteroidetes (Wilcoxon-Mann-Whitney |r|=0.33, P=5.1x10-3) and Proteobacteria (|r|=0.29; P=1.4x10-2). qPCR confirmed these findings (Prevotella buccalis fold change=130, P=2.1x10-4). Metagenomic inference revealed lower glycerolipid metabolism in exacerbated and stable asthmatic patients compared to controls (Kruskal-Wallis P=1.9x10-4). The nasal microbiome differs by asthma status, with enrichment of Proteobacteria and Bacteroidetes in subjects with asthma that is associated with lower glycerolipid metabolism. Our findings of these enriched taxa in nasal samples are consistent with lower airway findings, suggesting that microbiome profiling of easily-accessible nasal samples may be used to understand lower airway microbiota in asthma.

THE AIRWAYS MICROBIAL COMMUNITY COMPOSITION IN HEALTHY INDIVIDUALS AND BRONCHIAL ASTHMA PATIENTS

This review summarizes the results of studies on the composition of microbial communities in the airways of healthy individuals and patients with asthma. Modern molecular genetic technology of the microbial identification, which are based on a sequence determination of encoding proteins genes conserved regions. These regions form the 16s-subunit ribosomal RNA in microorganisms of different species. These genes are detected by sequencing markers characteristic of individual microorganisms and their phylogenetic groups, and allow to perform a deep analysis of the microbiota in healthy volunteers and patients with chronic bronchoobstructive diseases. So, apparently healthy human bronchial tree is characterized by low bacterial contamination (most typical representatives here are the genera Pseudomonas, Streptococcus, Prevotella, Fusobacteria and Veilonella, much less potentially pathogenic Haemophilus and Neisseria are represented). In bronchial asthma patients the lower respiratory tract microbiota undergoes a qualitative transformation: as compared to healthy individuals the number of Proteobacteria increases and the number of Bacteroidetes decreases. Severe asthma in children is associated with significant respiratory tract Staphylococcus spp. insemination. Association between the asthma developing higher risk in young children and organisms such as Haemophilus, Moraxella and Neisseria spp. It is of considerable interest to determine the role of the microbiome in the development of human diseases of the bronchopulmonary system, and to understand the impact of the microbes communities as a course of disease and the important factor for the development of resistance to therapy.

81 The concordance between the microbiome of the upper and lower respiratory tract is investigated in infants with cystic fibrosis

Background Nasopharyngeal (NP) and oropharyngeal samples (OP) are commonly used to direct therapy for lower respiratory tract (LRT) infections in non-expectorating infants with Cystic Fibrosis (CF). The level of concordance between microbiota of the upper respiratory tract (URT) and LRT in young children is, however, largely unknown. Objective To examine the concordance between URT and LRT microbiota in infants with CF. Methods Paired bronchoalveolar lavage fluid (BAL), NP and OP samples were longitudinally collected from 17 CF patients at the age of 3 and 12 months. We studied the concordance between the URT and LRT microbial communities by 16S-rRNA-based sequencing. Results Bacterial diversity is lower in NP compared to the OP and BAL samples. On group level, OP microbiota profiles showed more similarity with BAL microbiota compared to NP microbiota. However, potential pathogens like staphylococci , Moraxella and Haemophilus influenzae were almost exclusively observed in the NP but not in OP. Moreover, intraindividual concordance between both NP and OP microbiota profiles and paired BAL microbiota was limited. Conclusion At a population level, OP microbiota profiles resemble lung microbiota more closely than NP microbiota, however, potential respiratory pathogens are often detected in NP but not in OP samples. More importantly, within-individual concordance between the URT and LRT microbiome in CF patients is limited, restricting the diagnostic value of URT sampling during LRT infections in infancy. Whether microbiota profiling of BAL samples will indeed more reliably guide treatment of infections in CF infants compared to conventional culture remains to be studied.