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Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome
Arnaud Germain, … , Andrew Grimson, Maureen R. Hanson
Arnaud Germain, … , Andrew Grimson, Maureen R. Hanson
Published March 31, 2022
Citation Information: JCI Insight. 2022;7(9):e157621. https://doi.org/10.1172/jci.insight.157621.
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Research Article Metabolism

Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome

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Abstract

Post-exertional malaise (PEM) is a hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We monitored the evolution of 1157 plasma metabolites in 60 ME/CFS (45 female, 15 male) and 45 matched healthy control participants (30 female, 15 male) before and after 2 maximal cardiopulmonary exercise test (CPET) challenges separated by 24 hours, with the intent of provoking PEM in patients. Four time points allowed exploration of the metabolic response to maximal energy-producing capacity and the recovery pattern of participants with ME/CFS compared with the healthy control group. Baseline comparison identified several significantly different metabolites, along with an enriched percentage of yet-to-be identified compounds. Additionally, temporal measures demonstrated an increased metabolic disparity between cohorts, including unknown metabolites. The effects of exertion in the ME/CFS cohort predominantly highlighted lipid-related as well as energy-related pathways and chemical structure clusters, which were disparately affected by the first and second exercise sessions. The 24-hour recovery period was distinct in the ME/CFS cohort, with over a quarter of the identified pathways statistically different from the controls. The pathways that are uniquely different 24 hours after an exercise challenge provide clues to metabolic disruptions that lead to PEM. Numerous altered pathways were observed to depend on glutamate metabolism, a crucial component of the homeostasis of many organs in the body, including the brain.

Authors

Arnaud Germain, Ludovic Giloteaux, Geoffrey E. Moore, Susan M. Levine, John K. Chia, Betsy A. Keller, Jared Stevens, Carl J. Franconi, Xiangling Mao, Dikoma C. Shungu, Andrew Grimson, Maureen R. Hanson

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Figure 5

Venn diagram of the overlap analysis performed for each cohort between the 4 time points for metabolites statistically different between participants with ME/CFS and controls at P < 0.05.

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Venn diagram of the overlap analysis performed for each cohort between t...
The numbers shown are percentages to respect the proportionality between the smaller number of metabolites for the male cohort and both the female and total cohort, which have 3 times as many. Darkened percentages are the ones mentioned in the text.

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