A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease

Abstract

In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease.

Longitudinal survey of microbiome associated with particulate matter in a megacity

“…More importantly, although most of the species identified in PM 10 samples displayed significant differences in relative abundance between a low AQI level (I or II) and a high AQI level (IV or V), none in PM 2.5 exhibited such patterns (Wilcoxon rank-sum test, adjusted P < 0.1, Additional file 1: Tables 12). The microbes included those associated with human infections, such as Pseudomonas aeruginosa [26,27], with a positive correlation with pollutant concentration for both PM 2.5 and PM 10 samples (adjusted P < 0.05), and Stenotrophomonas maltophilia [28], with a positive correlation with the pollutant concentration in PM 10 samples. In addition, 72 microbes manifested prominent peaks in January (Additional file 2: Figure S12) when the air pollution was most severe.…”

Characterization of antibiotic resistance and host-microbiome interactions in the human upper respiratory tract during influenza infection

“…Previous studies have reported on the dynamics of antibiotic resistance expression in the gut and in the environmental microbiome, and have shown the diversity in ARG expression and niche specificity [10,22]. Other studies have shown the presence of ARGs in the lungs of cystic fibrosis patients [23], and in the stool of individuals who had never been exposed to antibiotics [24]. In our study, we identified bacteria-expressed genes that confer resistance to classes of antibiotics that the infected individuals were not taking, according to their antibiotic use history in the 12 months preceding influenza diagnosis.…”

Deciphering the Ecology of Cystic Fibrosis Bacterial Communities: Towards Systems-Level Integration

“…Relevant bacterial species in CF, such as P. aeruginosa [69] and Staphylococcus aureus [70,71], possess large, flexible gene pools, including genes encoding antibiotic resistance, pathogenicity, environmental response, and metabolic flexibility, which may explain the adaptive nature of chronic infections [72]. Although the metagenome contributes greatly to interactions with the host [25,73], very few studies on CF metagenomes have been performed, involving a limited number of both patients [29,63,74,75] and specific metabolic functions [76]. By analyzing the abundance of specific genes, such studies found a homogeneous distribution of predicted bacterial community activities (e.g., specific metabolic pathways) across patients with similar pulmonary function, as indicated by forced expiratory volume in 1 second (FEV 1 ) [73], suggesting a relationship between microbiome function and clinical status.…”

“…Although the metagenome contributes greatly to interactions with the host [25,73], very few studies on CF metagenomes have been performed, involving a limited number of both patients [29,63,74,75] and specific metabolic functions [76]. By analyzing the abundance of specific genes, such studies found a homogeneous distribution of predicted bacterial community activities (e.g., specific metabolic pathways) across patients with similar pulmonary function, as indicated by forced expiratory volume in 1 second (FEV 1 ) [73], suggesting a relationship between microbiome function and clinical status. This finding is in line with other metagenomic studies in humans and other systems, suggesting that changing the taxonomic composition does not drastically alter the functional capacity of the microbiome (see [77] for a comprehensive list of studies).…”