Plasma metabolomics reveals disrupted response and recovery following maximal exercise in ME/CFS, Arnaud Germain, Maureen R. Hanson et al, 2022

Just dropping in for a short bit - so much going on and trying to conserve mental energy.

I just reread the above old post of mine and I need to add more to the last paragraph to clarify that even though I would be able to manage a study at moderate level now and not get as severe a PEM that I would have experienced at severer levels but I would have to be extremely careful not to continue exerting at moderate level because that could trigger a spiral back to severer level. So there is always a delicate managing of the level I am at. I can get away with a bit of overdoing but I am very wary not to let it accumulate.

 

I recently joined this forum and am posting links to some of the analysis I've done in recent years. One big piece of work relates to this Hanson study.

I collected the data and put it online in a format that allows users to examine any metabolite.

https://jasemurphy.shinyapps.io/Germainetal2022/

The idea is this: if you see a metabolite or molecule mentioned in research or discussion, and you find yourself wondering whether it has been measured in me/cfs, you can look up this website to see how it behaved during Hanson's exercise provocation study. The data is presented visually in all its detail so you can see each subject and all 4 time points at which the data was measured.

This is the format of the site: a dropdown box at left where you choose the metabolite. and four barcharts at right showing each subject's result, medians and means. Patients in red and controls in blue; females then males. p values are given, uncorrected for multiple comparison.



There's many ways to improve on this - i'd like to show medians and means by sex, for example - one day maybe I will implement them.

 

I love this! I was having a look through this data anyway and a resource like this would make it so much easier! It would be great (if and when you ever feel like you wanted to) if you could visualise the data for each metabolite as a scatter plot/maybe with a violin: 4 strips for ME - 1 for each time point, and another 4 strips for HC. It would be a little easier to compare the group differences that way in my opinion. Maybe it could also have lines been the points for each individual so we can see the overall time course and correlation for each individual (or maybe it would look a bit cluttered)? Anyway, very cool

 

I wanted to make a post about this paper I think it's quite interesting. I like that by having a 4 time points and a longitudinal, paired design you partially mitigate problems with population noise.

At baseline the differences between patients and controls are fairly minimal but over the time course across the two CPETs there is an increasing difference in metabolites associated with glutamate, urea cycle, arginine and proline metabolism, and nitrogen metabolism just in general. This is a metabolite enrichment analysis showing pathways that differ between time points:



This is why I think some of the differences (and inconsistencies) we see across different metabolomics datasets could be due to an exercise effect. In Naviaux's paper they report differences in membrane lipids and differences in arginine and proline metabolism:


If you go into Naviaux' data you can see arginine and pyrroline-5-carboxylate (the precursor to proline) are among the most significant metabolites and some of the only ones to be positively correlated with severity.

In Lipkin and Fiehn's peroxisome metabolomics study however they replicate only the sphingolipids and not the nitrogen findings.

However, in Hanson's timecourse metabolomics study, they do report differences in both these metabolites, but only at the end of the time course, not at baseline.

 

In this figure panel they report on one of the top 2 significant metabolites associated with the difference between the first and second time point (before and after CPET 1). In controls this metabolite is elevated following exercise but unchanged in ME/CFS. This metabolite is unknown and has the placeholder name X15245.

I had a search to see if anything else was known about X15245, and it has since been identified in a separate screen by a different group in people with high liver fat content, and they report and association in a pathway with glutamate (another link to nitrogen metabolism being affected by exercise).

 

Brilliant. Thank you

 

given we know that females and males optimize energy sources differently, what does it look like re means/ medians/ p values if you look at males and females separately .There does seem to be a bit more variation for females?