Quantitative Analysis of the Human Airway Microbial Ecology Reveals a Pervasive Signature for Cystic Fibrosis

Deep sequencing of microbial marker genes in lung secretions revealed individualized microbiomes in healthy subjects that differed from stereotyped microbiomes of cystic fibrosis patients. There is There, There Although the absence of evidence is not necessarily evidence of absence,* scientists have generally considered the inability to culture microbes from tissues or other medical specimens to be evidence of sterility. For example, the health of the human lung has been defined in part by whether or not microbes are present. Now, Blainey et al. use high-throughput sequencing to survey microbes in sputum from control subjects and patients with the genetic disease cystic fibrosis (CF) and show that both groups have diverse, albeit different, microbial communities. Patients with CF suffer severe lung dysfunction and often die from respiratory failure. Mucus build-up in the lungs can cause life-threatening infections, which are treated by long courses of antibiotics. However, sometimes patients benefit clinically from this therapy even while their lungs continue to house bacteria. When the authors performed high-throughput pyrosequencing of 16S ribosomal DNA on sputum from 16 CF patients and 9 control individuals, they found that both groups of samples contained multiple microbial species. But CF patients displayed a different microbial ecology, most notably when one considered bacterial phylotypes that currently cannot be cultured in the lab. Although all patient samples did not contain an identical complement of organisms, all displayed a subset that constituted a microbial profile characteristic of CF. In fact, even when typical CF pathogens were excluded from the analysis, the microbial profiles still distinguished between control-subject and CF-patient samples. Similar findings were obtained from lung tissue taken from CF patients versus patients with other lung diseases. To bring the sequencing findings back to the clinic, the authors found that decreased microbial diversity correlated with the extent of inflammation in CF lungs. *Often attributed to cosmologist Martin Rees. Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the CF transmembrane conductance regulator. Disruption of electrolyte homeostasis at mucosal surfaces leads to severe lung, pancreatic, intestinal, hepatic, and reproductive abnormalities. Loss of lung function as a result of chronic lung disease is the primary cause of death from CF. Using high-throughput sequencing to survey microbes in the sputum of 16 CF patients and 9 control individuals, we identified diverse microbial communities in the healthy samples, contravening conventional wisdom that healthy airways are not significantly colonized. Comparing these communities with those from the CF patients revealed significant differences in microbial ecology, including differential representation of uncultivated phylotypes. Despite patient-specific differences, our analysis revealed a focal microbial profile characteristic of CF. The profile differentiated case and control groups even when classically recognized CF pathogens were excluded. As a control, lung explant tissues were also processed from a group of patients with pulmonary disease. The findings in lung tissue corroborated the presence of taxa identified in the sputum samples. Comparing the sequencing results with clinical data indicated that diminished microbial diversity is associated with severity of pulmonary inflammation within our adult CF cohort.