Inhabitants of the lungs with far-reaching importance

Bacterial lodgers also live in our respiratory system. © Mohammed Haneefa Nizamudeen/iStock

Similar to the intestines, peaceful bacteria also live in the lungs, which affect health in complex ways: Studies in animal models show that the lung microbiome influences immune reactions in the central nervous system, such as those that occur in multiple sclerosis. The results give hope that it might one day be possible to treat diseases of the central nervous system by influencing the lung-brain axis, the scientists say.

We are never really alone – our body is the habitat of a colorful community of myriad microorganisms. Research into these tiny lodgers has received a lot of attention in recent years. It has become increasingly clear what a complex role the microbiome plays in human health. In addition to many other effects, the composition of the bacterial communities also has an influence on the nervous system – connections to neurodegenerative diseases and psychological problems have been shown. So far, however, the focus has been on the body’s largest microbial habitat – the intestine. The team led by the University Medical Center Göttingen, on the other hand, has now devoted itself to researching the importance of the microbial inhabitants of the lungs. Compared to the intestines, our respiratory organs are only sparsely populated, but there is also a community of harmless bacterial species.

Is there also a lung-brain axis?

One of the basis of the study was evidence that impairments of the lungs can be associated with the development of neurological effects. For example, lung infections or smoking increase the risk of developing multiple sclerosis (MS). The special thing about it is that it is an autoimmune disease. The immune system and ultimately so-called T-cells mistakenly attack your own brain tissue in MS and cause damage there that leads to neurological deficits. Why and how the lungs could be involved in controlling autoimmune processes in the brain was previously unclear.

In order to explore a possible role of the lung flora, the researchers carried out studies on rats, which are used in multiple sclerosis research as models for the disease in humans: Through certain processes, they develop an inflammatory disease of the central nervous system, like MS – Have 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 desired, this had not led to elimination, but only to a slight change in the composition of the bacterial community in the lungs.

effects on the brain

The surprise came from the studies of the “MS disease state” of the model animals: the treatment had led to a reduction in symptoms – there were fewer inflammatory reactions in the central nervous system. Apparently, the change in the lung flora had led to this effect – but how? The researchers then pursued this question as detectives: step by step, they used a series of methods to investigate the location at which this influence is effective, which cells are affected there and which bacterial signals could be involved in regulating the immune effect.

They found that the antibiotic-mediated manipulation of the lung microbiome had an effect on the so-called microglia in the central nervous system. They are known as the “immune cells of the brain”. These are finely branched cells that can sense damage or threats from infectious agents and then sound the alarm to summon immune cells. As the studies showed, after the manipulation of the lung microbiome, the microglia changed their activity and even showed microscopically visible abnormalities. The cells also responded less strongly to inflammatory signals, which resulted in reduced recruitment of immune cells into the inflamed brain tissue of the test animals. This could explain the symptom relief, say the researchers.

Cell wall components affect immune surveillance in the brain

They then went in search of the bacterial signals that could trigger such “microglial pacification”. The key clue came from insights into which bacterial species the microbial community had evolved in favor of after antibiotic treatment. The analyzes revealed that species that have special cell wall components – lipopolysaccharides – had spread in the lung tissue. Further experiments then confirmed that these substances are actually decisive for the effect: an artificially increased amount of lipopolysaccharide in the lungs also caused the alleviating effect in the “MS model rats”. Targeted elimination of the substances, on the other hand, caused an increase in the symptoms of the autoimmune disease.

The study results now point to a previously unknown functional connection between the lungs and the brain, the scientists conclude. It can be assumed that the connections found in rats also occur in humans. However, to what extent this is actually the case must first be shown by additional studies and the further significance must also be explored, write Aubrey Schonhoff and Sarkis Mazmanian from the California Institute of Technology in Pasadena in an accompanying comment on the study: “The promising results should now be confirmed and expanded . This raises the question of whether the interactions between the lung microbiome and the microglia also influence other diseases that are associated with inflammation of the central nervous system.

As far as this is concerned, senior author Alexander Flügel from the University Medical Center Göttingen finally casts a hopeful look into the future: “It is possible that the lung-brain axis can even be used therapeutically. A targeted administration of probiotics or certain antibiotics could perhaps serve to influence the immune reactions of the brain and thus treat not only multiple sclerosis, but diseases of our central nervous system in general, in which the immune activity of the microglia plays a role,” says Flügel.

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

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