Respiratory microbiomes and lung cancer from mining communities

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Published: 21 Sep 2017
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Prof Luis Mur - Aberystwyth University, Aberystywth, Wales

Prof Luis Mur talks to ecancer at the Microbiome in Cancer and Beyond 2017 meeting about lung cancer and chronic obstructive pulmonary disease (COPD) which is particularly relevant to the mining districts of Wales. This is vital since early detection rates are as low as 5 %.

With assistance from the NHS, various samples are being collected to understand the biology of each microbiome, their relationship with lung cancer, and potential issues such as antibiotic resistance. Highly influential metabolites are identified and further studied with relation to the microbiome; these include short fatty acids, amides and sugars.

Dr Mur also describes the variation in between the upper and lower respiratory tracts, and how their relationships with lung cancer and COPD.

Dr Mur specialises in deriving drugs from natural sources, mainly due to some adverse effects and resistance arising from synthetic drugs. This future of this research looks very promising. 

What I’m working on is basically respiratory disease. I’m working on two major malignancies, really – lung cancer and chronic obstructive pulmonary disease. This is a major problem, particularly in Southern Wales because there’s a history there of mining, of course, and that obviously has ceased at the moment but the miners are getting older and so a lot of respiratory disease is coming to the fore. The Welsh Assembly is very much interested in tasking researchers throughout Wales to start looking at this problem and coming up with some novel, innovative approaches that actually could lead to detection of disease and in the case of lung cancer early detection. The detection figures for that are appalling, that’s why we’re getting such a poor prognosis. Five year prognosis is appalling – 5%, usually because it’s detected at what’s called stage 3 or stage 4 when basically you’re already spitting up blood, it’s much too late.

So I’m heavily involved with NHS Boards throughout Wales and we’re getting samples from patients, sputum primarily but also saliva. We also look at serum and urine and we’re busy identifying a whole range of markers from the clinical point of view but for us to actually find out some of the underlying biology and pathology that we can relate to clinical practice. That means detection and potentially some of the adverse effects of, for instance, some clinical treatments like antibiotic treatments. That is usually what is given in the first instance and so we see microbiomic changes leading to particularly pneumococcal changes which are multi-drug resistant and we can see that quite clearly when you look at the microbiome.

What influences on the respiratory tract have you identified?

What we find in respiratory tract is that the major influences are things like stage of development. In terms of metabolites we see a lot of changes, for instance, in sugars, short-chain fatty acids and amides in particular which influence what is going on in the microbiome. So we do very much a holistic approach, we take sputum, saliva and we identify what’s going on. What we find very clearly is that particularly certain bacteria are responding to amide changes that are progressive. So we can identify way down in stage 2 a clear difference from controls. Controls are basically from smokers because normal people will not produce sputum, for example.

So we’re doing all this and we find these are major drivers of the progression of the disease. There is an influence, of course, with smoking history, we can see that quite clearly. We do look at, for instance, occupational history but that does not seem to be a major factor in what we can see. But smoking history, smoking pack years, when you gave up all influence what the microbiome is doing, what the chemistry is doing and obviously the progression of the pathology. That’s true of lung cancer as much as COPD.

Do these vary by upper or lower regions?

They do. When we actually published the sputum effects some of the changes were rather suspicious because we look at spontaneous sputum. So basically we do look at lavage, so basically from bronchoscopies, but the vast majority of our patients are coming from spontaneous sputum so of course it comes from the mouth. So some of the changes we thought looked awfully a lot like upper respiratory tract. So we did a lot of recent examinations of the upper respiratory tract and we don’t see the same patterns there. We see that there are differences according to lung cancer, particularly micrococcal species, these are not seen in the lower respiratory tract. So again unique differences in the upper respiratory tract, in the buccal cavity, and also in the sputum. So these seem to be distinct. That is particularly the case of lung cancer; I know you’re an ecancer journal but in COPD it’s less clear, there seems to be much more interaction between what is going on in the buccal cavity into the lower respiratory tract as well. So lung cancer in particular seems to be a unique pattern and this seems to be reflecting in the kind of chemicals that are actually changing in the buccal cavity as opposed to in the lower respiratory tract.

Could you tell us about your work with deriving drugs from natural sources?

Again this basically a Welsh initiative, so let’s wave the Welsh dragon. They are actually looking at unmet clinical needs, so this is antibiotic drug resistance. I’ve already said that basically usual intervention by clinicians is to give them high dose usually amoxicillins. So in the microbiome you can see that there’s a huge change, for instance beta-lactamase increases and you also get aminoglycoside resistance genes. You can see TB increasing as well. So we basically have side projects which are hardly side projects anymore which are looking at TB. This is a pan-Wales effort involving Cardiff University and we’ve got at least two major leads which are basically very, very effective at actually killing TB in sputum, and this is multi-drug resistant TB. So this is involving looking at the medicinal history of the UK, China, India, Nigeria. We have projects all around the world and we actually look at respiratory relevant diseases and see if we can actually find natural products that actually could suppress them. We have been very successful in that and those have been taken forward with hopefully commercial interest.