Low Bacterial Diversity in Lungs Linked to Worse CF Outcomes
Absence of a dominant genus, more diversity indicative of better lung function
People with cystic fibrosis (CF) and advanced lung disease who have bacterial communities dominated by just one type of bacteria have a higher risk of lung transplant or death than those with more diverse communities, a study reports.
The risk of needing a lung transplant or death was increased by 80% in patients with low bacterial diversity, compared with those without a dominant genus — a median survival without needing a lung transplant of 1.6 years versus 2.9 years.
The study also found that, although most CF patients had low diversity communities with a dominant bacterial genus, nearly 40% of them didn’t and had lung communities with a richer bacterial diversity.
“A considerable proportion of pwCF [people with CF] with advanced lung disease do not have airway bacterial communities characterized by low diversity and a dominant genus and these individuals had better survival. An understanding of the antecedents of low diversity airway communities — and the impact these may have on lung disease trajectory — may provide avenues for improved management strategies,” the researchers wrote in the study, “Airway bacterial community composition in persons with advanced cystic fibrosis lung disease,” which was published in the Journal of Cystic Fibrosis.
The abnormal thick mucus in the lungs caused by CF can create an environment for bacteria to grow and proliferate. Because of this, people with CF often have recurrent lung infections, which can further damage them.
Studies have shown CF patients have lower bacterial diversity in their lungs than people without CF, and that this diversity can decrease with age and inflammation.
Bacterial diversity in the lungs and clinical outcomes
A research team at the University of Michigan Medical School studied lung bacterial communities in people with CF and advanced lung disease to assess the link between bacterial diversity and clinical outcomes and find out whether bacterial diversity is associated with disease progression.
The researchers used sputum (phlegm) samples from 190 CF patients collected during routine medical care between April 2000 and July 2020. All the patients had advanced lung disease, defined in the study as having a percent predicted forced expiratory volume in one second (ppFEV1) of 40 or lower during the year prior to collecting the sample. This value represents how much air is forcefully expelled in one second and is a common measure of lung function.
Samples weren’t used if the patient was taking antibiotics for a pulmonary exacerbation, an acute worsening of lung symptoms, because “antibiotics for [pulmonary exacerbations] significantly alters lung microbial communities thereby confounding assessment of baseline community structure,” the researchers said.
The composition of the bacterial community was assessed through bacterial gene sequencing. A genus was considered dominant if it occurred at least twice as much as the second most abundant genus. Samples with a dominant genus were defined as having low bacterial diversity.
The most frequently detected bacterial genera were those associated with CF, such as Pseudomonas and Staphylococcus, and those known to colonize upper airways, such as Streptococcus and Rothia.
Results showed 115 (60.5%) CF patients had low diversity communities in their sputum with no dominant genus in the bacterial communities of the remaining 75 (39.5%). In 104 (90%) low-diversity samples, the dominant genus was one associated with CF, most frequently Pseudomonas and Staphylococcus. In 53 (70%) samples without a dominant genus, the one with the greatest relative abundance was associated with CF.
Median survival without needing a lung transplant was 1.6 years for CF patients with lung communities dominated by one bacterial genus, compared with 2.9 years for those with more diverse communities. This corresponded to an 80% increased risk of lung transplant or death in those with low bacterial diversity, a hazard ratio of 1.8.
The lack of a dominant genus, greater bacterial diversity, and the presence of Staphylococcus aureus susceptible to the antibiotic methicillin were all significantly associated with better lung function, according to analyses that evaluated the associations between bacterial composition and lung function.
Conversely, a greater relative abundance of a dominant genus, pulmonary exacerbation, and higher number of antibiotic courses taken in the year before the sample collection were negatively associated with lung function.
The study found that a sizable proportion of patients with advanced lung disease have relatively diverse lung bacterial communities, even though CF is often characterized by low bacterial diversity, and that these patients have a lower risk of death or lung transplant.
“The factors that drive decreasing community diversity require elucidation, but are likely multifactorial and include antibiotic therapy,” the researchers wrote, adding that “whether strategies aimed at maintaining more diverse airway communities have potential to improve clinical outcomes requires a more complete understanding of the complex relationship(s) between disease severity, antibiotic use, and bacterial community structure.”
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