MEA Research Update: Metabolomics and ME/CFS – Dr Morten and the Oxford research centre 13th August 2018

MeSci

MeSci

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The ME Association has been working for some time with Dr Karl Morten and the research team at Oxford who have recently been honing their approach to the study of metabolomics in ME/CFS.

Before embarking on a new study utilising samples from the ME/CFS Biobank for the ME Association, they have been conducting research using samples from a patient cohort in Poland.

https://www.meassociation.org.uk/20...-the-oxford-research-centre-13th-august-2018/
 
Interesting stuff.

A mysterious metabolite came up in their analysis.

Basal metabolic rate (BMR) is the rate of body energy expenditure over time. Initial comparisons indicate that basal metabolic rate is strongly correlated with two unidentified metabolites, that do not have accepted chemical names in the metabolomics database. However, as variables such as age and BMI are well known to have an impact on basal metabolic rate we attempted to control for these variables whilst analysing males and females separately. Males were found to have a higher average BMR and when correcting the correlation for age and BMI and using a form of regression analysis, these confounded the correlation with basal metabolic rate. Conversely, following these corrections, previously insignificant metabolites exhibit significant correlations. Without correcting for confounding factors (age and BMI) none of the metabolites with high VIP scores correlated with fatigue scores. However, with confounder correction using partial regression analysis to account for these factors, one of the unknown metabolites showed a strong correlation.
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I don't understand what they did here exactly but it seems that whatever kind of exercise this was didn't affect the metabolic alterations. I remember that least year they reported that GET appeared to have a negative impact on energy production. It sounds like this was a CPET, in which case it has nothing to do with GET.

We also studied the effect of an incremental exercise programme on a sub-group of patients and were able to examine how exercise affected the metabolic profile in blood. We found the exercise programme to be useful in simulating increased physical exertion and therefore as a means to isolate changes in metabolism that may result specifically from increased locomotor (movement) output. The programme increased an individual’s amount of physical activity in increments – a similar approach as Graded Exercise Therapy (GET) – but with the intensity of the prescribed exercise based on parameters such as VO2 max (the volume of oxygen used by the body during maximal exercise). To measure this, subjects were asked to pedal on a stationary exercise bike (ergometer), until they could no longer sustain their maximal attained energetic output (measured in watts) by completing a test referred to as cardiopulmonary exercise testing (CPET). This provided a global indication of the integrated response to exercise of the pulmonary (lungs), cardiovascular (heart), haematopoietic (blood components), central nervous system (CNS) and skeletal muscle systems. Comparison of the metabolic profile of ME/CFS plasma samples taken before and after exercise showed no significant differences between these time points. This suggested that exercise was unable to significantly alter the metabolome within the ME/CFS patient cohort. Put simply, this indicates that the lesser-on-average amount of exercise/mobility experienced by patients is not likely a key mediator of the metabolic perturbations observed in ME/CFS.
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It looks like they have some really interesting findings already including differences between pwME and healthy controls. It's great that they had access to a lot of clinical data and blood samples from a Polish clinic. That meant they could relate the blood metabolites to things like tilt table test data and exercise data. They are looking at subgrouping, and picking the most interesting metabolites to look at in the much larger set of samples from the UK ME biobank, with the hope of finding biomarkers.

That mysterious unidentified metabolite has me intrigued. I guess there are so many possible organic molecules, not all are in the databases.

Exciting stuff.
 
MeSci said:
Doesn't this conflict with what Ron Davis found? I can't think where it is - I think it's on this site somewhere, and also on Phoenix Rising - he found a lot of differences.
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This research found differences between patients and controls, but no differences when comparing metabolic profiles of patients before and after an exercise stress test (it is a bit unclear what they did exactly, but that's my interpretation).

Hanson et al is doing similar work but hasn't published yet I believe.
 
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