Implications of the Lung Microbiota for GI Disease and Human Health

For many years, the lungs were considered to be sterile and free from colonization by bacteria. Bacterial DNA that was detected in the lungs was thought to result from technical contamination, and challenges associated with growing microbes from airway samples were attributed to the absence of microbes rather than technical limitations due to culture conditions. However, it is now known that the lungs of a healthy human contain a bacterial microbiota maintained through a balance of microbial immigration from the upper respiratory track and elimination by host defense mechanisms.

Are bacteria found in healthy lungs?

In general, six major genera inhabit the airways of healthy lungs: Prevotella, Streptococcus, Veillonella, Fusobacterium, Porphyromonas and Neisseria. The microbial biomass is generally low. When the immigration of bacteria to and reproduction of bacteria within the lungs exceeds the airway’s ability to clear these microbes, the density of the microbiota increases and its composition can change, potentially leading to respiratory illness.

Different respiratory conditions are characterized by dominant bacteria species. For example, Cystic Fibrosis involves the excessive growth of P. aeruginosa, S. aureus and Burkholderia species while idiopathic pulmonary fibrosis is characterized by Haemophilus, Veillonella, Streptococcus and Neisseria. Eosinophilic asthma features Streptococcus, T. whipplei, Actinomycetaceae and Enterobacteriaceae.

Interestingly, the composition of the lung microbiota has implications that extend beyond the respiratory tract, since it could be related to the function and dysfunction of cells within the gastrointestinal tract and vice versa. Up to 50% of inflammatory bowel disease patients also have impaired lung function which often manifests after the onset of gastrointestinal illness.

Soluble microbial components and metabolites that are transported through the circulation are one method by which microbiota in the gut and those in the lungs could communicate and have implications for the behavior of the immune system.

Administrating bacteria or their key molecular components into the gastrointestinal tract of mice, whether via the oral route or other means, has shown benefit for the resolution of lung infections. Injection of lipopolysaccharide, a component of gram-negative bacteria, into the gastrointestinal tract of antibiotic-treated mice restored their ability to generate an immune response against infections within the lungs. Intranasal inoculation of bacterial strains that activate Nod2 receptors has been shown to protect mice against certain respiratory infections, and oral supplementation with C. orbiscindens protected mice against infection with influenza virus.

However, some bacteria do not have a positive effect and instead exacerbate illness. For example, Ruminococcus gnavus can lead to a worsening of respiratory allergies. Thus, much is yet to be revealed regarding the microbial gut-lung axis, and microbiome-focused therapies should be approached carefully only when there is sufficient data to support their application.

Furthermore, fungi, protozoa, helminths, viruses, and phages, which are known to impact the gut microbiota, may have indirect consequences on respiratory health. Little is known about their role in this context and perhaps additional research should be dedicated to this field.

The role of the microbiome in human health is certainly fascinating, and further research into the role of gut and lung microbiota in particular human diseases has the potential to help us develop better preventative measures and therapies.

Wypych, T.P., Wickramasinghe, L.C. & Marsland, B.J. The influence of the microbiome on respiratory healthNat Immunol 20, 1279–1290 (2019).

Learn more about the latest research in the field of immunology.