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Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model.

ABSTRACT: Cystic fibrosis transmembrane conductance regulator deficient mouse models develop phenotypes of relevance to clinical cystic fibrosis (CF) including airway hyperresponsiveness, small intestinal bacterial overgrowth and an altered intestinal microbiome. As dysbiosis of the intestinal microbiota has been recognized as an important contributor to many systemic diseases, herein we investigated whether altering the intestinal microbiome of BALB/c Cftr(tm1UNC) mice and wild-type littermates, through treatment with the antibiotic streptomycin, affects the CF lung, intestinal and bone disease. We demonstrate that streptomycin treatment reduced the intestinal bacterial overgrowth in Cftr(tm1UNC) mice and altered the intestinal microbiome similarly in Cftr(tm1UNC) and wild-type mice, principally by affecting Lactobacillus levels. Airway hyperresponsiveness of Cftr(tm1UNC) mice was ameliorated with streptomycin, and correlated with Lactobacillus abundance in the intestine. Additionally, streptomycin treated Cftr(tm1UNC) and wild-type mice displayed an increased percentage of pulmonary and mesenteric lymph node Th17, CD8?+?IL-17+ and CD8?+?IFN?+ lymphocytes, while the CF-specific increase in respiratory IL-17 producing ?? T cells was decreased in streptomycin treated Cftr(tm1UNC) mice. Bone disease and intestinal phenotypes were not affected by streptomycin treatment. The airway hyperresponsiveness and lymphocyte profile of BALB/c Cftr(tm1UNC) mice were affected by streptomycin treatment, revealing a potential intestinal microbiome influence on lung response in BALB/c Cftr(tm1UNC) mice.

SUBMITTER: Bazett M

PROVIDER: S-EPMC4709690 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model.

Bazett Mark M Bergeron Marie-Eve ME Haston Christina K CK

Scientific reports 20160112

Cystic fibrosis transmembrane conductance regulator deficient mouse models develop phenotypes of relevance to clinical cystic fibrosis (CF) including airway hyperresponsiveness, small intestinal bacterial overgrowth and an altered intestinal microbiome. As dysbiosis of the intestinal microbiota has been recognized as an important contributor to many systemic diseases, herein we investigated whether altering the intestinal microbiome of BALB/c Cftr(tm1UNC) mice and wild-type littermates, through ...[more]

PMID: 26754178

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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

Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model.

Publications

Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model.

Similar Datasets

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