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Cystic Fibrosis Shifts Lung Microbiome

09/27/2012
Megan Scudellari

Healthy lungs are teeming with a broad array of microbes. Lungs of patients with cystic fibrosis, on the other hand, have markedly less diversity.


Scientists used to believe that lungs are a sterile organ, since few microbes had ever been cultured from healthy lungs. But a new study, published yesterday in Science Translational Medicine, reveals a teeming rainforest of bugs in our lungs—and a surprising lack of that diversity in the lungs of patients with cystic fibrosis (1).

Actinobacteria (above) are more prevalent in the lungs of patients with cystic fibrosis than in healthy lungs. Credit: GrahamColm, Wikipedia





“Our work confirms a suspicion that people have had for a long time that lungs are really nowhere near sterile,” said David Cornfield, a pediatric pulmonologist at the Stanford Cancer Institute and author of the study. The results suggest that cystic fibrosis (CF) patients may benefit from a probiotic regimen.

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The lungs of patients with CF are prone to life-threatening infections because of the build-up of unusually thick, sticky mucus that makes a perfect breeding ground for bacteria. Cornfield and colleagues at Stanford University set out to assess which microbes are most present in lungs of CF patients, and how that microbe community differs from healthy lungs.

The team collected sputum samples from 16 CF patients and nine healthy individuals, and sequenced the ribosomal DNA of the microbes in each sample. The ability to distinguish between human and microbial DNA has long been a challenge, said Cornfield, but co-authors Paul Blainey and Stephen Quake designed and implemented a high-throughput sequencing method that accurately determined the source of each species. “It provided highly reliable information on the microbial identifies,” said Cornfield.

To be sure they were identifying microbes from the lungs, and not just the sputum, the team also examined lung tissue from seven patients who had lung transplants: three with cystic fibrosis and four with other lung diseases.

Across all the samples, the team identified a wide variety of organisms in healthy lungs, including many microbial species that have never before been cultured in a laboratory.

They also identified specific bacterial phyla that dominate in each setting. The microbial profile of lungs from CF patients is so distinct, the authors write, that it alone can be used to distinguish between an individual with CF and one without.

It is possible that microbes that play a positive role in healthy lungs get outcompeted by harmful bacteria in lungs of CF patients, said Cornfield. And that suggests a possible therapeutic intervention: “It poses the question of whether or not we ought to do more to enhance certain microbes in the lungs,” he said. Today, most CF patients take broad-spectrum antibiotics to keep lung infections at bay, but Cornfield envisions a treatment plan where doctors target bad bacteria with specific antibiotics while simultaneously supplementing good bacteria with probiotics.

Next, Cornfield plans to study the microbiome in lungs of CF patients across many ages, to see if diminishing microbial diversity correlates with lung function.

References

1. Blainey, P.C., et al. 2012. Quantitative Analysis of the Human Airway Microbial Ecology Reveals a Pervasive Signature for Cystic Fibrosis. Sci Trans Med. 4(153): 153ra130.

Keywords:  metagenomics genomics