Stanton Bruce A.

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Stanton
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Bruce A.
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  • Article
    Analysis of lung microbiota in bronchoalveolar lavage, protected brush and sputum samples from subjects with mild-to-moderate cystic fibrosis Lung Disease
    (Public Library of Science, 2016-03-04) Hogan, Deborah A. ; Willger, Sven D. ; Dolben, Emily L. ; Hampton, Thomas H. ; Stanton, Bruce A. ; Morrison, Hilary G. ; Sogin, Mitchell L. ; Czum, Julianna ; Ashare, Alix
    Individuals with cystic fibrosis (CF) often acquire chronic lung infections that lead to irreversible damage. We sought to examine regional variation in the microbial communities in the lungs of individuals with mild-to-moderate CF lung disease, to examine the relationship between the local microbiota and local damage, and to determine the relationships between microbiota in samples taken directly from the lung and the microbiota in spontaneously expectorated sputum. In this initial study, nine stable, adult CF patients with an FEV1>50% underwent regional sampling of different lobes of the right lung by bronchoalveolar lavage (BAL) and protected brush (PB) sampling of mucus plugs. Sputum samples were obtained from six of the nine subjects immediately prior to the procedure. Microbial community analysis was performed on DNA extracted from these samples and the extent of damage in each lobe was quantified from a recent CT scan. The extent of damage observed in regions of the right lung did not correlate with specific microbial genera, levels of community diversity or composition, or bacterial genome copies per ml of BAL fluid. In all subjects, BAL fluid from different regions of the lung contained similar microbial communities. In eight out of nine subjects, PB samples from different regions of the lung were also similar in microbial community composition, and were similar to microbial communities in BAL fluid from the same lobe. Microbial communities in PB samples were more diverse than those in BAL samples, suggesting enrichment of some taxa in mucus plugs. To our knowledge, this study is the first to examine the microbiota in different regions of the CF lung in clinically stable individuals with mild-to-moderate CF-related lung disease.
  • Preprint
    Iron supplementation does not worsen respiratory health or alter the sputum microbiome in cystic fibrosis
    ( 2013-10) Gifford, Alex H. ; Alexandru, Diana M. ; Li, Zhigang ; Dorman, Dana B. ; Moulton, Lisa A. ; Price, Katherine E. ; Hampton, Thomas H. ; Sogin, Mitchell L. ; Zuckerman, Jonathan B. ; Parker, H. Worth ; Stanton, Bruce A. ; O'Toole, George A.
    Iron supplementation for hypoferremic anemia could potentiate bacterial growth in the cystic fibrosis (CF) lung, but clinical trials testing this hypothesis are lacking. Twenty-two adults with CF and hypoferremic anemia participated in a randomized, double-blind, placebo-controlled, crossover trial of ferrous sulfate 325 mg daily for 6 weeks. Iron-related hematologic parameters, anthropometric data, sputum iron, Akron Pulmonary Exacerbation Score (PES), and the sputum microbiome were serially assessed. Fixed-effect models were used to describe how ferrous sulfate affected these variables. Ferrous sulfate increased serum iron by 22.3% and transferrin saturation (TSAT) by 26.8% from baseline (p < 0.05) but did not affect hemoglobin, sputum iron, Akron PES, and the sputum microbiome. Low-dose ferrous sulfate improved hypoferremia without correcting anemia after 6 weeks. We did not observe significant effects on sputum iron, Akron PES, and the sputum microbiome. Although we did not identify untoward health effects of iron supplementation, a larger blinded randomized controlled trial would be needed to fully demonstrate safety.
  • Article
    The microbiome in pediatric cystic fibrosis patients : the role of shared environment suggests a window of intervention
    (BioMed Central, 2014-04-28) Hampton, Thomas H. ; Green, Deanna M. ; Cutting, Garry R. ; Morrison, Hilary G. ; Sogin, Mitchell L. ; Gifford, Alex H. ; Stanton, Bruce A. ; O’Toole, George A.
    Cystic fibrosis (CF) is caused by mutations in the CFTR gene that predispose the airway to infection. Chronic infection by pathogens such as Pseudomonas aeruginosa leads to inflammation that gradually degrades lung function, resulting in morbidity and early mortality. In a previous study of CF monozygotic twins, we demonstrate that genetic modifiers significantly affect the establishment of persistent P. aeruginosa colonization in CF. Recognizing that bacteria other than P. aeruginosa contribute to the CF microbiome and associated pathology, we used deep sequencing of sputum from pediatric monozygotic twins and nontwin siblings with CF to characterize pediatric bacterial communities and the role that genetics plays in their evolution. We found that the microbial communities in sputum from pediatric patients living together were much more alike than those from pediatric individuals living apart, regardless of whether samples were taken from monozygous twins or from nontwin CF siblings living together, which we used as a proxy for dizygous twins. In contrast, adult communities were comparatively monolithic and much less diverse than the microbiome of pediatric patients. Taken together, these data and other recent studies suggest that as patients age, the CF microbiome becomes less diverse, more refractory to treatment and dominated by mucoid P. aeruginosa, as well as being associated with accelerated pulmonary decline. Our studies show that the microbiome of pediatric patients is susceptible to environmental influences, suggesting that interventions to preserve the community structure found in young CF patients might be possible, perhaps slowing disease progression.