The Power of the Lung Microbiome

The lungs, with a surface area about 30 times that of skin, are in constant dialogue with the outside world. Until just over a decade ago, they were considered sterile. High-throughput sequencing overturned this theory in 2010, showing diverse lower airway microbial communities that shift with disease.

Research into the lung microbiome is still in its early stages compared to the more developed studies of other body microbiomes. Initially, scientists investigated how microbial colonization might impact pulmonary allergies. However, most research focused on the gut and fecal microbiomes. The sterile lung believe persisted until 2010, when researchers identified the composition of airway microbiota, revealing the presence of a respiratory microbiome. Technologies such as computed tomography (CT) scans, PCR, and 16S rRNA sequencing, have since allowed for deeper investigation. Since 2011, research has progressively explored the links between lung diseases and the microbiome, initially focusing on conditions like cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD). This research confirmed the microbiome exists even in healthy individuals, and that it changes in disease states. However, clinical applications still remains limited. Most clinical microbiome work has focused on CF, a condition that affects just over 4,500 Canadians. In contrast, non CF bronchiectasis is now recognised as the third most common chronic lung disease (affecting >500 people per 100,000 in Europe and North America), and is far less studied, with virtually no Canadian adult data.

The Thornton lab, established in May 2023, explores how the lower respiratory tract microbiome informs diseases like bronchiectasis, drawing from lessons from CF. The lab established new technologies, including Oxford Nanopore Sequencing – a small platform collapsing weeks-long culture and resistance testing into a 24-hour window with real-time base calling, metagenomic classification, resistance screening and automated reporting. All this aims to enable clinicians to tailor personalized therapy faster. In collaboration with Dr. Braedon McDonald (critical care), this technology is being applied as a more rapid test to better understand the lung microbiome during periods of health compared to disease in patients. The overarching goal is to develop a rapid, user-friendly pipeline for microbiome analysis to personalize therapeutics as part of a clinical toolkit.

Building this infrastructure required broad support: the inaugural Snyder Institute Catalyst Grant (co-PIs Drs. Thornton and McDonald) provided proof of concept funds followed by a Canada Foundation for Innovation John R. Evans Leaders Fund award and Department of Medicine start up fund to install sequencers, high performance computing nodes and laboratory equipment, as well as generous patient directed gifts from the Summit Foundation and the CF community.

The same platform drives the lab’s satellite projects including: 

• CIHR Team Grant research interrogating the microbiology of wildfire smoke: the sequencing of particulate matter across Western Canada to catalogue viable bacteria, fungi and phage capable of hitch hiking on smoke plumes.
• CF Canada and CF Foundation supported research: long-read sequencing studying other diseases, such as CF, to understand the role of fungi – in particular Candida species, along with the microbiome. 

In combination with the wet lab research, the Thornton lab also founded and manages the Canadian Bronchiectasis and Non-tuberculous mycobacterium (NTM) registry (along with Dr. Julie Jarand) which is Canada’s first clinical registry and in collaboration with the US and Europe, to better understand the prevalence and epidemiology of these diseases.

The ultimate goal is to make precision antimicrobial and anti-inflammatory strategies routine for the tens of thousands of Canadians living with bronchiectasis, effectively turning complex microbial ecology into an everyday clinical tool.