Heady days: Review charts growth of lung microbiome research

In 2010 scientists reported for the first time that microbiota – the community of microorganisms that includes bacteria – existed in the airways of humans; they were met with disbelief: the healthy lung was thought to be sterile.

Around the same time, Professor Ben Marsland and colleagues conducted a study demonstrating that administration of innocuous bacteria to the lungs of mice protected them against asthma. A further study together with Professor Nicola Harris showed that ‘germ-free’ mice, which are bred under sterile conditions and have no microbiota, exhibited increased susceptibility to asthma.

While the idea of the gut microbiome had already gained traction, convincing a scientific audience of the existence of a lung microbiome proved an uphill challenge.

“At the time it was very hard to raise funds for this research, it took a number of years to change the dogma that the airways were sterile. It was a tough few years,” said Professor Marsland, head of the Central Clinical School’s Respiratory Immunology laboratory. “But following the data and making discoveries, even if against preconceived ideas, is one of the most exciting parts of being a scientist.”

A leader in what is now a well-established field, Professor Marsland was asked recently to write a review of current knowledge on the lung microbiome, which appeared this week in the high-impact journal Nature Immunology.

“There’s been a huge advance in our understanding of how the microbiota influences respiratory diseases over the last few years. The review was an opportunity to bring these advances together and provide some clarity to where we stand, and where the field is going,” he said.

Research into microbiota in the body dates back to the 17th Century when Dutch scientist Antonie van Leeuwehoek discovered bacteria living in his oral cavity and faeces, the review said. The potential importance of van Leeuwehoek’s observations was overlooked for more than 200 years, until a flourish of microbiology research in the second half of the 19th century, including that of Louis Pasteur.

Widespread access to high-throughput DNA sequencing technology in 2005 initiated a revolution in microbiota research, with exponential growth in reports on host–microbe interactions.

Professor Marsland said there have been two major conceptual advances in the field.

The first was in the description of the microbes in the lung and that the type of microbes differ between health and disease.

“In addition, the airway microbiota develops during the first two post-natal months, and as it develops it influences the maturation of the immune system. The types of bacteria we are exposed to in life shape the functionality of the cells in our lungs.”

Professor Marsland’s lab published a world-first study documenting this in 2018.

He has made a number of other major advances in the field. In 2014, in work published in Nature Medicine, Professor Marsland and his team showed that that formation of the lung microbiome ‘educated’ the immune system of mice, and could protect them against the development of asthma.

The second major advance made in the field relates to the so-called ‘gut-lung axis’.

“Not only do microbes in the lungs influence respiratory diseases, but the microbiota in the gut can also have an effect.”

Professor Marsland’s team published further papers in Nature Medicine in 2014 and Immunity in 2018, showing that diet influenced the gut microbiota, haematopoiesis and ultimately lung responses against allergens and viruses.

With insights made into the characteristics of the microbiome and how it affects the immune system, interest has turned to how information such as this could be used clinically.

Professor Marsland said that current thinking is that researchers were still some way from trying to get probiotics in the airways to protect against disease but that clinical studies were testing whether microbial metabolites – the factors that microbes produce – may have beneficial effects. Studies are also probing whether microbial components have the potential to protect against airway disease.

“There is clearly translational potential of work investigating the microbiota which is exciting to be part of,” he said.

Professor Marsland said the other challenge ahead for the field lay in interrogating the other micro-organisms present in the microbiota. “Nearly all the research to date has been focussed on bacteria. Bacteria are the main component of the microbiome but fungi, viruses, phages and helminths (worms) are all very important players too.”

Tomasz Wypych and Lakshanie Wickramasinghe were co-authors on the paper, which reported on the findings of 185 papers.

https://www.nature.com/articles/s41590-019-0451-9