DZL scientists at the BREATH site in Hanover have studied the airways of patients with cystic fibrosis and analysed the genetic information of all microorganisms living there, the so-called microbial metagenome. They showed that patients' microbial metagenome differs from healthy individuals at a very early stage and continues to change individually in each patient.
From age four, a specific composition of the lung metagenome can be observed in patients with cystic fibrosis. However, the children still have normal lung function and do not harbour the usual cystic fibrosis pathogens. Then, as they get older, the pathogens typical of the disease, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, colonise the lungs and the proportion of microbes found in healthy individuals decreases. This depletion happens differently depending on the patient and results in each person with cystic fibrosis having an individual microbial metagenome unique in the number and composition of the microorganisms living there.
“Our study shows for the first time that the imbalance of the microbiome in lung diseases can be recognised by a deficiency of certain microorganisms," says Prof. Dr. Burkhard Tümmler, coordinator of the disease area "Cystic Fibrosis (Cystic Fibrosis)" at the DZL site in Hannover. "This finding could create a starting point for new therapies in cystic fibrosis."
Together with his team, Tümmler investigated the microbial metagenome of the oral cavity and the upper and lower respiratory tract of 65 people with cystic fibrosis aged 7 to 60 years for the current study and compared it for the first time with the microbial communities of healthy people. To do this, the scientists performed comprehensive deep sequencing from nasal lavage samples, nasal and throat swabs, and sputum samples. Sputum is the secretion of the deep airways that enters the throat when coughing. Using a specially developed method, they could clearly identify organisms that occur only rarely and are difficult to cultivate. Together with a previous study on metagenome data sets in young children, the published data form a comprehensive and representative representation of the microbiome of all age groups within the current cystic fibrosis patient population.
Cystic fibrosis (CF) is a congenital metabolic disease caused by genetic defects that affect the salt balance of the affected person. This causes thick mucus, which blocks the lungs' airways and internal organs, such as the intestines. The mucus obstructs breathing in the lungs and serves as a breeding ground for bacteria, fungi, viruses, or parasites. This leads to chronic infections, inflammations, and remodeling processes in the respiratory tract, significantly influencing the course of the disease.
"It remains to be seen whether the lifelong intake of CFTR modulators will change the temporal development of the metagenome in the airways," says Tümmler about the current triple therapy with CFTR modulators in cystic fibrosis. Recent studies show that this treatment leads to less viscous airway secretions and a decrease in inflammation and bacterial infection in the lungs in patients with cystic fibrosis.
Pienkowska K, Pust MM, Gessner M, Gaedcke S, Thavarasa A, Rosenboom I, Morán Losada P, Minso R, Arnold C, Hedtfeld S, Dorda M, Wiehlmann L, Mainz JG, Klockgether J, Tümmler B. The Cystic Fibrosis Upper and Lower Airway Metagenome. Microbiol Spectr. 2023 Mar 9;11(2):e0363322. doi: 10.1128/spectrum.03633-22.