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

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 card...

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Main 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
Format: Article
Language:English
Published: American Society for Clinical investigation 2022-05-01
Series:JCI Insight
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Online Access:https://doi.org/10.1172/jci.insight.157621
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author 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
author_facet 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
author_sort Arnaud Germain
collection DOAJ
description 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.
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spelling doaj.art-973e7d0184904965933651861f8c0d1a2022-12-22T03:32:57ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-05-0179Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndromeArnaud GermainLudovic GiloteauxGeoffrey E. MooreSusan M. LevineJohn K. ChiaBetsy A. KellerJared StevensCarl J. FranconiXiangling MaoDikoma C. ShunguAndrew GrimsonMaureen R. HansonPost-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.https://doi.org/10.1172/jci.insight.157621Metabolism
spellingShingle 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
Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome
JCI Insight
Metabolism
title Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome
title_full Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome
title_fullStr Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome
title_full_unstemmed Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome
title_short Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome
title_sort plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis chronic fatigue syndrome
topic Metabolism
url https://doi.org/10.1172/jci.insight.157621
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