Chronic obstructive pulmonary disease (COPD), also known as emphysema, is the 4-5th commonest cause of death in Australia and the world and there are no effective treatments. It has an enormous socioeconomic burden worldwide. It is induced by chronic cigarette smoking, which leads to chronic inflammation, the progressive destruction of lung tissue, declining lung function and COPD. The “microbiome” describes all of the microbes that exist in an individual and new technologies enable the complete profiling of microbiomes in health and disease. We, and others, propose that a healthy microbiome protects against, whereas an altered one promotes inflammatory diseases, including COPD/emphysema. There is substantial immune cross talk between the gut and lung. We propose that modifying the gut microbiome may be a novel therapy for COPD. Microbiomes can be modified by microbial transfer, selective antibiotics and/or probiotics and their metabolic products, which effectively control other disease. The manipulation of the microbiome in COPD has not been investigated.
Our previous work & preliminary data:
It is very difficult and expensive to study microbiome changes as disease develops in humans, especially in chronic diseases such as COPD. Up until recently studies were also difficult as it took 6 months to induce COPD in models with cigarette smoke. Over the last 6 years we have developed a novel short-term cigarette smoke-induced model of COPD. This enables such studies of the role of the microbiome in COPD for the first time. In ground-breaking studies we have shown that gut and lung microbiomes are altered in experimental COPD. We have gone on to show that gut microbiomes can be transferred between models simply by co-housing them (they eat each other’s poo). Remarkably we have now shown that co-housing smoke-exposed and control models protect the smoking models against the development of COPD. Conversely the non-smoking models start to show signs of airway inflammation. We have now identified 2 virtually unknown bacteria that go from 0% to 10% of the gut microbiome in smoking models. These are reduced to 2.5% in co-housed smoke-exposed models and increased to 2.5% in co-housed non-smoking models. This clearly identifies these 2 bacteria as culprits in the development of COPD that we may be able to target with specific antibiotics. In addition, we have found 2 other bacteria, which have the opposite relationships and may have beneficial effects in COPD. We may be able to use these bacteria as probiotics in the treatment of COPD. In other studies we have also shown that the development of COPD was completely inhibited by adding bacterial metabolic products (acetate) to the drinking water of models.
These results open up many new avenues for research for us and we are only limited by funding.
The next steps:
We now aim to determine the role and potential for modulating microbiomes and their products as new therapies for COPD. We now aim to;
- Characterise changes in the microbiome during the progression and exacerbations (as well as induction) of COPD, as well as during standard treatments with steroids and antibiotics in models.
- Assess for the same changes in gut microviomes in people with mild to moderate to severe COPD compared with healthy people.
- Design, develop and use specific antibiotics to prevent and treat changes in microbiomes and as new treatments for COPD