Chronic infections with the pathogen Pseudomonas aeruginosa change the lung microbiome in CF-patients / Early detection and treatment of infections could prevent a deterioration in lung function / A close-up of the airway ecosystem / Publication in “European Respiratory Journal”

Contrary to previous assumptions the airways, including the lung, are not sterile but exhibit an ecologic niche for a variety of microorganisms similar to the known ecosystem of the bowel, though the composition of the airway microorganisms is still partly unknown. If the genetic material of all the microbes (= microbiome) in our lungs is in balance, we feel healthy. If, however, harmful microorganisms dominate, infections of the lung and reduced lung function ensues. The important question is what comes first? An out of balance microbiome that opens the door to pathogens or a causal chronic infection with specific bacteria that supersedes the normal microbiome? This fundamental question with regard to cystic fibrosis patients has now been solved by Prof. Alexander Dalpke, Deputy Chief Physician of the Department of Microbiology and Hygiene and Prof. Marcus A. Mall, Head of the Cystic Fibrosis Center at University Hospital Heidelberg (both DZL site TLRC). “Our findings show that changes in the microbiome are a consequence and not the cause of chronic infection with the bacteria Pseudomonas aeruginosa”, says Prof. Dalpke. Evidence of initial or regular detection of P. aeruginosa was obtained by repeated sampling of the airways of cystic fibrosis patients during quarterly routine check-ups and at times of hospitalization. The study received funding from the German Center for Lung Research (DZL) and has recently been published in the “European Respiratory Journal”.

Microbiome characterization by genome sequencing

In patients suffering from the hereditary multi-organ disease cystic fibrosis the mucus in the airways is dehydrated and more viscous than in healthy humans. The clearance of such abnormally thick and sticky mucus by transport along the ciliated airway epithelium is impaired and offers a rich breeding ground for the bacterium Pseudomonas aeruginosa, the culprit of infections that rapidly lead to a deterioration of lung function in cystic fibrosis patients. Traditionally, Pseudomonas infections are detected by cell culture methods. However, for this study the Heidelberg scientists sequenced the genes of the microorganisms (=microbiome) to assess the microorganism composition of airway samples. Using this approach it was possible to determine the microbiome from patients that were chronically, intermittently or never infected with Pseudomonas aeruginosa. “An initial infection treated aggressively with antibiotics could protect patients not only from a chronic infection but also prevent further unwanted changes in the microbiome”, explains Dalpke. Importantly, once a chronic Pseudomonas infection is established it can usually only be suppressed and not eliminated with antibiotics because the bacteria tend to hide behind a protective biofilm. “Children with cystic fibrosis remain Pseudomonas-free for longer after very early onset treatment and we found fewer changes in the microbiome”, summarized the microbiologist, Prof. Dalpke.

More than 100 types of bacteria can be found in the lung – what is their function?

n total, 392 airway samples from 71 patients were investigated. Thanks to the close cooperation with the Children’s Pulmonology Division of the University Hospital Heidelberg infants, for which data is rare, were also sampled. The results demonstrate that the microbiome can consist of more than 100 different types of bacteria, and the composition may vary significantly from patient to patient. It is still unclear whether the microorganisms of the upper airways that colonize the lung over the course of a lifetime may have a protective effect. Prof. Dalpke: “Potentially, microorganisms of the upper airways such as bacteria of the type Neisseria, Veillonella and Pretovella may be associated with a better lung function. This is currently hotly debated and subject to further research”.

 

 

Further information / Sources:

Press release from the University Hospital Heidelberg

Original-Publication:

Boutin S, Graeber SY, Stahl M, Dittrich AS, Mall MA, Dalpke AH. Chronic but not intermittent infection with Pseudomonas aeruginosa is associated with global changes of the lung microbiome in cystic fibrosis. Eur Respir J 2017 50: 1701086. https://doi.org/10.1183/13993003.01086-2017

Contact, DZL site Heidelberg, TLRC:

Prof. Dr. Alexander Dalpke
Zentrum für Infektiologie
Medizinische Mikrobiologie und Hygiene
Universitätsklinikum Heidelberg
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