Supplemental Oxygen May Alter Lung Microbiome in CF Patients

Sputum samples suggest harmful changes in bacteria, fungi diversity

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

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Supplemental oxygen lessened the abundance of some microbial species in sputum samples from people with cystic fibrosis (CF) while sparing others, including Pseudomonas aeruginosa and Staphylococcus aureus, the main causes of bacterial lung infections in patients, a study reported.

A need for caution exists when using supplemental oxygen, “historically … considered a benign medical intervention,” since it could have harmful consequences on the airway microbiome — the lungs’ microbe population — of CF patients.

“Supplemental oxygen use may enable the growth of lung pathogens and should be further studied in the clinical setting,” the researchers wrote.

Their study, “Supplemental Oxygen Alters the Airway Microbiome in Cystic Fibrosis,” was published in the journal mSystems.

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Thick mucus builds in the lungs of CF patients, affecting breathing and promoting lung infections. Supplemental oxygen is commonly given when blood oxygen levels become too low. In fact, “supplemental oxygen is prescribed for approximately 11%” of all patients, the researchers noted, and its use “traditionally viewed as simply a marker of disease severity rather than a contributor to disease progression.”

An increasing number of preclinical studies, however, have reported toxic effects of excessive oxygen. These include lung injury and a less active immune system. Oxidative stress — an imbalance between oxygen reactive species and antioxidants in the body — and injury to pulmonary cells were pointed to as possible causes of these effects.

Harmful bacteria may flourish in lung microbiome with oxygen

Researchers, led by those at Massachusetts General Hospital, questioned whether supplemental oxygen changes the airway microbiome in people with CF.

“The role of the pulmonary microbiome in health may run parallel to that of the gut microbiome, where alterations to microbial composition and diversity [following antibiotic treatment] may lead to subsequent consequences in terms of clinical health,” the team wrote.

The airway microbiome is made up of communities of bacteria, fungi, and viruses living in the respiratory tract. In CF patients, low microbial diversity in the sputum, a thick substance coughed up from the lungs, has been linked with worse lung function and disease progression, as the microbiome becomes dominated by Pseudomonas.

Eleven patients, with an average age of 29.2, were recruited from that hospital’s Adult Cystic Fibrosis Center between November 2019 and March 2020. To determine how hyperoxia — the excess supply of oxygen — affects airway microbiota, the researchers cultured their sputum samples, collected at outpatient center visits, under 21%, 50%, and 100% oxygen conditions.

They then used an approach called shotgun metagenomic sequencing to perform a genetic analysis of all the organisms present in each sample.

Findings showed that hyperoxia decreased the absolute abundance of some bacteria, such as Rothia mucilaginosa, Streptococcus species, and Actinomyces oris. But hyperoxia had no effect on the absolute abundance of Pseudomonas aeruginosa and Staphylococcus aureus.

Anaerobes, bacteria able to survive without oxygen, such as Rothia mucilaginosa, are considered part of a balanced microbial community. A previous study showed that an attack community — microbial populations that trigger strong immune responses — and a reduced relative abundance of Rothia were associated with pulmonary exacerbations, or respiratory symptom flares, in CF.

In the current study, hyperoxia also decreased alpha diversity — the variety of microbes in a sample — of the airway microbiome.

Two types of fungi, Candida albicans and Aspergillus fumigatus, were eliminated with 100% oxygen.

Other changes induced by hyperoxia included reductions in predicted microbial community function, predicted antimicrobial resistance genes, and mobile genetic elements — genetic material that can either move around within a genome or jump across different genomes.

“Oxygen supplementation may disrupt the airway microbiome by promoting growth of canonical CF pathogens such as Pseudomonas and S. aureus while depleting anaerobes and fungi,” the scientists wrote.

“Thus, it may be prudent for clinicians to monitor sputum microbial communities following initiation of supplemental oxygen for emergence of harmful pathogens,” they added.

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