Lung inhabitants of far-reaching importance –

Just like the gut, peaceful bacteria also live in the lungs, which affects health in a complex way: Studies in animal models show that the lung microbiome influences immune responses in the central nervous system, such as those found in multiple sclerosis. The results offer hope that one day it will be possible to treat diseases of the central nervous system by influencing the brain-lung axis, the researchers said.

We are never really alone – our body is home to a colorful community of countless microorganisms. In recent years, much attention has been paid to research on these small tenants. It is becoming increasingly clear how the microbiome plays a complex role in human health. In addition to many other effects, the composition of bacterial communities also affects the nervous system – links with neurodegenerative diseases and psychological problems have been shown. Until now, however, the focus has been on the body’s largest microbial habitat – the gut. On the other hand, a team led by the University Medical Center of Göttingen has now dedicated itself to researching the importance of the microbes inhabiting the lungs. Our respiratory organs are sparsely populated compared to our intestines, but there is also a community of harmless species of bacteria.

Is there also a brain-lung axis?

One of the foundations of the study was evidence that impaired lung function may be related to the development of neurological effects. For example, a lung infection or smoking increases your risk of developing multiple sclerosis (MS). The special feature is that it is an autoimmune disease. In MS, the immune system and ultimately the so-called T cells mistakenly attack your own brain tissue and cause damage there that leads to neurological deficits. Why and how the lungs might be involved in controlling autoimmune processes in the brain was previously unclear.

To investigate the possible role of lung flora, scientists conducted studies on rats, which are used in studies of multiple sclerosis as models of human disease: As a result of certain processes, inflammatory diseases of the central nervous system, such as multiple sclerosis, develop – get sick. The scientists then treated these model animals with low doses of the antibiotic neomycin which was administered directly into the lungs. Subsequent analyzes showed that, as requested, this did not lead to an elimination, but only a slight change in the composition of the bacterial community in the lungs.

effect on the brain

The study of the “MS disease state” in model animals was a surprise: treatment led to a reduction in symptoms – there were fewer inflammatory responses in the central nervous system. Apparently, the change in lung flora led to this effect – but how? The researchers then addressed this question as detectives: step by step, they applied a series of methods to investigate where the effect was effective, which cells were affected there, and which bacterial signals could be involved in regulating immune function.

They found that the manipulation of the lung microbiome via antibiotics had an effect on the so-called microglia in the central nervous system. These are known as “brain immune cells”. These are finely branched cells that sense damage or threats from infectious agents, then alarm to summon immune cells. Research has shown that after manipulating the lung microbiome, the microglia changed its activity and even showed microscopically visible abnormalities. Cells were also less responsive to inflammatory signals, which resulted in reduced recruitment of immune cells to the inflammatory brain tissue of the test animals. That could explain the relief of symptoms, the researchers said.

Components of the cell wall influence immune surveillance in the brain

They then went on to look for bacterial signals that could trigger this “pacification of the microglia.” The key clue came from an insight into which species of bacteria the microbial community had evolved following treatment with antibiotics. The analyzes showed that species with special components of the cell wall – lipopolysaccharides – have spread in the lung tissue. Further experiments then confirmed that these substances were indeed decisive for the effect: an artificially increased amount of lipopolysaccharide in the lungs also produced a soothing effect in “MS model rats”. In turn, deliberate elimination of these substances increased the symptoms of autoimmune disease.

Research results now point to a previously unknown functional connection between the lungs and the brain, the researchers conclude. It can be assumed that the combinations occurring in rats also occur in humans. However, to what extent this is the case must first be demonstrated by additional research, and further relevance must also be explored, write Aubrey Schonhoff and Sarkis Mazmanian of the California Institute of Technology in Pasadena in a comment accompanying the study: the promising results should now be confirmed and extended . This raises the question of whether interactions between the pulmonary microbiome and microglia also affect other CNS diseases.

Regarding this, senior author Alexander Flügel of the University Medical Center of Göttingen finally gives a hopeful glimpse into the future: “It is possible that the brain-lung axis could even be used therapeutically. Targeted administration of probiotics or certain antibiotics could possibly influence the immune responses of the brain and thus treat not only multiple sclerosis but also diseases of our central nervous system in general, in which microglia immune activity plays a role. ” says Flügel.

Source: Universitätsmedizin Göttingen, specialist article: Nature, doi: 10.1038 / s41586-022-04427-4

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