Discover the hidden ecosystem of microorganisms living in our lungs and how they influence respiratory health and disease.
Imagine an organ that was considered sterile for decades, now known to pulse with an invisible ecosystem. The lung, responsible for gas exchange, hosts a complex community of microorganisms that significantly regulate our health. The discovery of the lung microbiome is revolutionizing pulmonology and shedding new light on the development and treatment of widespread diseases such as asthma, COPD, and cystic fibrosis. This article dives into the hidden world of the smallest inhabitants of our airways and deciphers how a delicate bacterial balance determines health and disease.
The lung microbiome refers to the totality of all microorganisms - bacteria, viruses, and fungi - that live in our airways. Strictly speaking, science distinguishes between "microbiota" (the microorganisms themselves) and "microbiome" (the genetic material of these microbes and their interactions with the human body), though in practice the terms are often used interchangeably 5 .
Compared to the gut, which hosts about 38 trillion bacteria, the lung is much less populated with approximately 10³ to 10⁵ bacteria per gram of lung tissue. The reason is the sparse nutrient availability that makes survival difficult for microbes. The represented species mostly belong to Proteobacteria, Firmicutes, and Bacteroidetes 5 .
Colonization of the lung begins with the first breaths after birth. The first bacteria can be detected in the airways just a few hours after birth. Their initially unstructured composition becomes increasingly diverse in the first seven weeks of life and stabilizes thereafter 5 .
Important influencing factors in early development include:
Similar to the gut, commensal ("good") bacteria prevent the settlement of pathogens 5 .
Microbes communicate via surface proteins and metabolites such as short-chain fatty acids with the human immune system 5 .
Some scientists view the lung as an "ecosystem network" where bacteria interact with each other and with viruses and fungi 5 .
In the healthy lung, a simple basic rule applies: although numerically few, but species-diverse bacteria settle 1 .
When the lung becomes diseased, this ratio reverses: significantly more bacteria can be detected, but they are dominated by few species. The microbial density increases, while diversity decreases. This imbalance in the microbial ecosystem is referred to by experts as dysbiosis 1 .
In people with asthma bronchiale, the microbial community of the lung is composed differently than in healthy individuals. Proteobacteria, Firmicutes (especially Streptococcus), Bacteroidetes (especially Prevotella), and Actinobacteria dominate 1 .
Researchers from Lausanne found in animal experiments that the temporal development of the microbiome could be crucial for the development of asthma 1 .
Even in very early disease stages, increased bacteria of the genera Streptococcus, Staphylococcus, Prevotella, and Gemella can be found in the COPD lung, which although belong to the normal microbiome in the oral cavity, hardly belong in the lung 1 .
The state of the microbiome changes with the disease course: particularly in exacerbation phases, it is significantly less complex and dominated by potentially pathogenic germs 1 .
In the metabolic disease cystic fibrosis, a viscous mucus forms in the airways, fundamentally changing the living conditions for microbes. In adult affected individuals, a significantly reduced species diversity can be detected, with pathogenic bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa dominating 1 .
Researchers found that these typical shifts develop around the age of three to four years, which could indicate a decisive therapeutic time window 1 .
In idiopathic pulmonary fibrosis, a chronic scarring of lung tissue, more pathogenic pathogens are found in the microbiome of the airways than in lung-healthy individuals, especially Haemophilus, Neisseria, and Streptococcus 1 .
Current studies show that in an acute disease episode, both certain viruses and bacterial dysbiosis play a previously underestimated role 1 .
A recent study by German and Swedish research teams investigated how pneumonia caused by pneumococci changes the microbiome of the nasopharynx - and how long these changes last 2 .
The scientists analyzed the microbiome of 122 individuals: one half suffered from pneumococcal pneumonia, the other half was healthy and served as a comparison group. The ill individuals were examined both during the acute phase of pneumonia and three months after the infection 2 .
The researchers found that the balance of the microbiome in the nasopharynx was still significantly disturbed three months after the survived infection. Also, the way certain bacteria interacted with each other during and after the infection differed significantly from healthy individuals 2 .
This persistent dysbiosis could play a central role in how well the body can defend against future pathogens - and thus also in the prevention of new infections. The study suggests that a past pneumonia can throw the microbiome off balance long-term and weaken the immune system 2 .
The study of the lung microbiome places special demands on methodology, as the bacteria occur in relatively small numbers and samples are difficult to obtain. Modern techniques have brought decisive progress here .
Collection of samples without contamination by oral and throat flora
Detection and identification of microorganisms via their genetic material
Highly sensitive identification of bacterial species in samples with low biomass
Quantification of bacterial density in the lung
Evaluation of complex microbial communities and their interactions
How the genetics of the host influences the lung microbiome is a relatively new research area. A research team of the Leibniz ScienceCampus "EvoLUNG" investigated this question in the mouse model and identified seven gene regions for eight bacterial characteristics .
The scientists found several promising genes associated with immune and inflammatory responses, lung function, and disease susceptibility. It was shown that the amount of Lactobacilli in the lung is strongly associated with a gene region that contains the gene for the anti-inflammatory messenger interleukin-10 (IL-10) .
IL-10 knockout mice actually had fewer Lactobacilli than animals without this genetic defect. These results provide the first evidence for a role of the genetic variation of the host that contributes to changes in the composition of the lung microbiome .
The composition of the lung microbiome could help predict the disease course in critically ill patients in the future. A study in the American Journal of Respiratory and Critical Care Medicine showed that intensive care patients who had many bacteria in the lung on the first day after admission needed ventilation more frequently in the further course 8 .
In individuals whose treatment was less effective, two bacterial species that normally occur in the gut were found more frequently in the lung microbiome - Lachnospiraceae and Enterobacteriaceae spp. The presence of Enterobacteriaceae in the lung was also associated with an increased risk of acute respiratory distress syndrome (ARDS) 8 .
The targeted influence of the lung microbiome opens up new therapeutic perspectives. Research approaches include:
Especially for immunocompromised population groups, therapies aimed at a healthy microbiome could be a promising addition to the treatment of respiratory infections in the future 2 .
The study of the lung microbiome has fundamentally changed our understanding of lung health. What began with the discovery that the lung is not sterile is developing into a paradigm-shifting concept in pulmonology. The delicate balance between human and microbe proves to be a decisive factor for health and disease.
Future research will show to what extent targeted modulation of the microbiome - for example by administering probiotics or other innovative therapies - can be used therapeutically. One thing is already certain: the small inhabitants of our lung have great importance for our health.