Cystic Fibrosis (CF) is a disease that mainly affects the lungs and arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes for the CFTR membrane protein located on certain secretory cells. CFTR dysfunction leads to complications such as the production of abnormally viscous mucus which causes chronic suppurative lung infections that require antibiotics to treat. New drugs called CFTR modulators can help improve CFTR protein function and some are even FDA-approved for use in children. In addition to CFTR protein function, the lung’s resident microbiota and its richness of diversity, plays an important role in both health and disease, including CF.
In a new study published in Heliyon, scientists from Children’s National Hospital examined the difference in the upper airway microbiome between children with CF and healthy controls. Age-related differences among children with CF and the impact of CFTR modulators on microbial diversity were also assessed. Seventy-five children between 0-6 years of age participated in the study, including 25 children with CF and 50 healthy controls. For CF participants, oropharyngeal swabs and clinical data were obtained from the biorepository, while data for controls were obtained during a single clinical visit.
Analysis revealed that CF patients had less microbial diversity and different composition of the upper airway microbiome compared to age similar controls, a finding that is consistent with research on the lower airways. Despite having less overall microbial richness, children with CF displayed a greater presence of Staphylococcus species, (a main driver of the pulmonary exacerbations characteristic of CF), three Rothia operational taxonomic units (OTUs) and two Streptococcus OTUs. CF patients received a significantly higher number of antibiotics courses within the previous year compared to healthy controls, and further investigation will be necessary to understand the impact of antibiotics on the upper airway microbiome of infants and children with CF.
Longitudinal comparisons to study effects of age and CFTR modulation on the microbiome of children with CF were also undertaken. Younger CF patients (those 0 to <3 years of age at study enrollment), were more likely to have culturally-normal respiratory flora and more stable microbial composition over time than older CF patients (those ≥ 3–6 years of age at study enrollment), with no significant differences in alpha or beta diversity. Older CF patients were significantly more likely to be receiving a CFTR modulator than younger patients. CF patients receiving CFTR modulators had higher microbial diversity measures than those not receiving CFTR modulators and were closer (but still significantly lower) in microbial richness to healthy controls. No significant differences in beta diversity were found between the three groups.
This study adds to the growing body of evidentiary support for the use of CFTR modulators in improving airway microbial diversity in CF patients. Future studies with a larger cohort and greater focus on the impact on early initiation of CFTR modulators on microbial diversity and clinical outcomes is necessary.
The study, “Airway microbial diversity is decreased in young children with cystic fibrosis compared to healthy controls but improved with CFTR modulation,” was recently published in Heliyon. The lead author is Andrea Hahn, M.D., M.S., an investigator at the Children’s National Research Institute. Notable authors include Aszia Burrell; Emily Ansusinha; Hollis Chaney, M.D.; Iman Sami, M.D.; Geovanny F. Perez, M.D.; Anastassios C. Koumbourlis, M.D., M.P.H.; Robert McCarter, Sc.D.; and Robert J. Freishtat, M.D., M.P.H..