In-Depth: Links Between Microbiota and the Gut-Lung Axis

What is the Lung Microbiome?

The lung microbiome, found in the lower respiratory tract, is a collection of microorganisms, particularly found on the mucous layer and the epithelial surfaces. It was traditionally believed that the lungs of healthy individuals were sterile when examined by culture-based techniques. However, advances in molecular identification techniques have led to the ability to greater explore the lung microbiome. Initial studies have demonstrated that the lower respiratory tract has a detectable microbial population that may be altered in disease. This emerging and exciting field of investigation is leading to new ways of thinking about the lung and about lung disease.

Human Microbiome Definitions:

To begin to understand investigations of the lung microbiome, sharing precise definitions has become increasingly important.

Microbe – Any microscopic lifeform Microbiome – The collection of microorganisms (microbes), their genes, and their environmental interactions Microbiota – All of the microorganisms (microbes) of a given region or habitat Metagenome – Genetic information of the microbiota Microbial Communities – Populations of microbes that interact functionally and metabolically Dysbiosis – An imbalance in the composition of the microbiota

The Gut Microbiome

The gut microbiome, commonly known as intestinal flora, consists of trillions of microorganisms. These microorganisms are mainly bacteria, but eukaryotes, eukaryote viruses and cells, genes and metabolites from them can also be found. The gut microbiome aids digestion and the absorption and synthesis of nutrients. It is also known to impact metabolic functions, immune responses in our body, body weight, brain function and mood. The gut microbiome is unique to each person, and begins to develop very early in life. Diet plays an important role in determining the composition of the gut microbiota, where gut microorganisms help to assimilate dietary nutrients, which are otherwise indigestible. Changes in dietary patterns can have an effect on the gut microbiota and lead to the development of intestinal disorders, such as diabetes, obesity, colon cancer and inflammatory bowel disease.

The Gut-Lung Axis

The bi-directional cross-talk that occurs between the gut and the lung has been termed the Gut-Lung axis. Intestinal disturbances have been observed in certain lung diseases, which have been shown to be mediated by the gut microbiota and some probiotics have shown beneficial effects on lung health and the treatment of respiratory diseases. It stands to reason that a deeper understanding of the gut microbiome and its role in respiratory disorders will aid in the design and development of improved, novel drugs for the treatment of lung diseases.

The Gut Microbiome and Lung Disorders

It is important to understand the influence of gut microbiota on the functioning of various organs within the body. A nutrient-rich diet supplemented with dietary fibres is associated with a more diverse gut microbiota. Human health is significantly influenced by the metabolites produced by the gut microbiome during the digestion of food, and there is a known association between dysbiosis in gut microbiota and malnutrition. The metabolites produced by the gut microbiota not only modulate gastro-intestinal immunity, but also impact distal organs like lung and brain. Changes occur when the metabolites reach the lungs. Hence, dysbiosis in gut microbiota has been implicated in several lung diseases, including asthma, cystic fibrosis and allergy.

Changes in dietary patterns, including unhealthy diets consisting of cured and red meats, refined grains and junk foods, and the subsequent effect on gut microbiota can also impair lung function and are implicated in disorders of the lung, and increase the risk of respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma and respiratory infections. Equally, people suffering with COPD can improve their condition and lung function by switching to a diet high in fruit, vegetable, fish and wholegrains. Reduction in Bifidobacteria and an increase in Clostridia in the intestine are associated with asthma in early life. In addition, studies in rodents have shown that antibiotic intake leads to a depletion of certain species within the gut microbiota and in turn influences lung diseases and allergic inflammation.

The Lung Microbiome and Intestinal Disorders

Research into the lung microbiome and its effect on distal organs has been less researched, but is emerging as an important area for drug development with the discovery that changes in the lung microbiome also influence the composition of the gut microbiome. There is growing evidence, in animal studies, that pneumonia due to multi drug resistant Staphylococcus aureus or Pseudomonas aeruginosa is likely to stimulate intestinal inflammation. Further animal studies have shown that dysbiosis in the lung microbiota by the administration of a lipopolysaccharide is followed by disturbances in gut microbiota, which is caused by the bacteria moving from the lung into the bloodstream. Also, studies in mice have shown that the influenza virus increases Enterobacteriaceae and reduces Lactobacilli and Lactococci in the intestinal microbiota. Thus, there is much evidence to show that the gut and lung are complexly linked organs and that the gut-lung axis is a bidirectional loop, with each organ influencing the homeostasis of the other.

The Lung Microbiome and Lung Disorders

Research has shown that a disruption in the lung microbiota plays an important role in the pathophysiology of lung inflammatory disorders. However, its role in health and disease is currently only poorly understood. As such, scientists are looking towards the lung microbiota and characterising its composition as a prognostic marker or as a target for drug therapy in chronic lung diseases.

An analysis of the bronchoalveolar lavage in children with severe asthma has shown a difference in microbiota community in comparison to control subjects. There is a greater abundance of certain flora, with the lung microbiota being more diverse and abundant in some subjects with asthma. Determining the mechanisms underlying lung microbiota maintenance is paramount in finding novel methods to prevent respiratory diseases, such as asthma.

Conclusions

The lung microbiome is a rapidly growing area of research, where furthering our understanding of the lung microbiota can aid in drug discovery with the potential elucidation of novel mechanisms and therapeutic targets. The subsequent influence of the lung microbiota on the immune system, might also lead to the identification of important discoveries into the pathogenesis of lung diseases, as well as the potential role the lung microbiome may play in distal organs, like the gut, and associated diseases. The gut and lung microflora are clearly linked by nutrition, the immune system and digestive and respiratory health, through mutual communication linking this intricate system.

References

Anand S & Mande SS (2018) Diet, Microbiota and Gut-Lung Connection. Front Microbiol 9:2147.

Costa AN et al. (2018). The Pulmonary Microbiome: Challenges of a New Paradigm. J Bras Pneumol. Jul 30:0

Dumas A et al. (2018) The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases. Cell Microbiol 20(12):e12966.

Mathieu E et al. (2018) Paradigms of Lung Microbiota Functions in Health and Disease, Particularly, in Asthma. Front Physiol 9:1168.