Dataset Information

Longitudinal Associations of the Cystic Fibrosis Airway Microbiome and Volatile Metabolites: A Case Study.

ABSTRACT: The identification of 16S rDNA biomarkers from respiratory samples to describe the continuum of clinical disease states within persons having cystic fibrosis (CF) has remained elusive. We sought to combine 16S, metagenomics, and metabolomics data to describe multiple transitions between clinical disease states in 14 samples collected over a 12-month period in a single person with CF. We hypothesized that each clinical disease state would have a unique combination of bacterial genera and volatile metabolites as a potential signature that could be utilized as a biomarker of clinical disease state. Taxonomy identified by 16S sequencing corroborated clinical culture results, with the majority of the 109 PCR amplicons belonging to the bacteria grown in clinical cultures (Escherichia coli and Staphylococcus aureus). While alpha diversity measures fluctuated across disease states, no significant trends were present. Principle coordinates analysis showed that treatment samples trended toward a different community composition than baseline and exacerbation samples. This was driven by the phylum Bacteroidetes (less abundant in treatment, log2 fold difference -3.29, p = 0.015) and the genus Stenotrophomonas (more abundant in treatment, log2 fold difference 6.26, p = 0.003). Across all sputum samples, 466 distinct volatile metabolites were identified with total intensity varying across clinical disease state. Baseline and exacerbation samples were rather uniform in chemical composition and similar to one another, while treatment samples were highly variable and differed from the other two disease states. When utilizing a combination of the microbiome and metabolome data, we observed associations between samples dominated Staphylococcus and Escherichia and higher relative abundances of alcohols, while samples dominated by Achromobacter correlated with a metabolomics shift toward more oxidized volatiles. However, the microbiome and metabolome data were not tightly correlated; examining both the metagenomics and metabolomics allows for more context to examine changes across clinical disease states. In our study, combining the sputum microbiome and metabolome data revealed stability in the sputum composition through the first exacerbation and treatment episode, and into the second exacerbation. However, the second treatment ushered in a prolonged period of instability, which after three additional exacerbations and treatments culminated in a new lung microbiome and metabolome.

SUBMITTER: Hahn A

PROVIDER: S-EPMC7198769 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Longitudinal Associations of the Cystic Fibrosis Airway Microbiome and Volatile Metabolites: A Case Study.

Hahn Andrea A Whiteson Katrine K Davis Trenton J TJ Phan Joann J Sami Iman I Koumbourlis Anastassios C AC Freishtat Robert J RJ Crandall Keith A KA Bean Heather D HD

Frontiers in cellular and infection microbiology 20200428

The identification of 16S rDNA biomarkers from respiratory samples to describe the continuum of clinical disease states within persons having cystic fibrosis (CF) has remained elusive. We sought to combine 16S, metagenomics, and metabolomics data to describe multiple transitions between clinical disease states in 14 samples collected over a 12-month period in a single person with CF. We hypothesized that each clinical disease state would have a unique combination of bacterial genera and volatile ...[more]

PMID: 32411616

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Project description:Features of the airway microbiome in persons with cystic fibrosis (pwCF) are correlated with disease progression. Microbes have traditionally been classified for their ability to tolerate oxygen. It is unknown whether supplemental oxygen, a common medical intervention, affects the airway microbiome of pwCF. We hypothesized that hyperoxia significantly impacts the pulmonary microbiome in cystic fibrosis. In this study, we cultured spontaneously expectorated sputum from pwCF in artificial sputum medium under 21%, 50%, and 100% oxygen conditions using a previously validated model system that recapitulates microbial community composition in uncultured sputum. Culture aliquots taken at 24, 48, and 72 h, along with uncultured sputum, underwent shotgun metagenomic sequencing with absolute abundance values obtained with the use of spike-in bacteria. Raw sequencing files were processed using the bioBakery pipeline to determine changes in taxonomy, predicted function, antimicrobial resistance genes, and mobile genetic elements. Hyperoxia reduced absolute microbial load, species richness, and diversity. Hyperoxia reduced absolute abundance of specific microbes, including facultative anaerobes such as Rothia and some Streptococcus species, with minimal impact on canonical CF pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus. The effect size of hyperoxia on predicted functional pathways was stronger than that on taxonomy. Large changes in microbial cooccurrence networks were noted. Hyperoxia exposure perturbs airway microbial communities in a manner well tolerated by key pathogens. Supplemental oxygen use may enable the growth of lung pathogens and should be further studied in the clinical setting. IMPORTANCE The airway microbiome in persons with cystic fibrosis (pwCF) is correlated with lung function and disease severity. Supplemental oxygen use is common in more advanced CF, yet its role in perturbing airway microbial communities is unknown. By culturing sputum samples from pwCF under normal and elevated oxygen conditions, we found that increased oxygen led to reduced total numbers and diversity of microbes, with relative sparing of common CF pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus. Supplemental oxygen use may enable the growth of lung pathogens and should be further studied in the clinical setting.

Dataset Information

Longitudinal Associations of the Cystic Fibrosis Airway Microbiome and Volatile Metabolites: A Case Study.

Publications

Longitudinal Associations of the Cystic Fibrosis Airway Microbiome and Volatile Metabolites: A Case Study.

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