Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise

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dc.citation.issue17
dc.citation.volume26
dc.contributor.authorSharma S
dc.contributor.authorHodges LD
dc.contributor.authorPeppercorn K
dc.contributor.authorDavis J
dc.contributor.authorEdgar CD
dc.contributor.authorRodger EJ
dc.contributor.authorChatterjee A
dc.contributor.authorTate WP
dc.contributor.editorOltra E
dc.date.accessioned2025-10-03T00:43:37Z
dc.date.available2025-10-03T00:43:37Z
dc.date.issued2025-09-03
dc.description.abstractPost-exertional malaise (PEM) is a defining symptom of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), yet its molecular underpinnings remain elusive. This study investigated the temporal–longitudinal DNA methylation changes associated with PEM using a structured two-day maximum repeated effort cardiopulmonary exercise testing (CPET) protocol involving pre- and two post-exercise blood samplings from five ME/CFS patients. Cardiopulmonary measurements revealed complex heterogeneous profiles among the patients compared to typical healthy controls, and VO2 peak indicated all patients had poor normative fitness. The switch to anaerobic metabolism occurred at a lower workload in some patients on Day Two of the test. Reduced Representation Bisulphite Sequencing followed by analysis with Differential Methylation Analysis Package-version 2 (DMAP2) identified differentially methylated fragments (DMFs) present in the DNA genomes of all five ME/CFS patients through the exercise test compared with ‘before exercise’. With further filtering for >10% methylation differences, there were early DMFs (0–24 h after first exercise test) and late DMFs between (24–48 h after the second exercise test), as well as DMFs that changed gradually (between 0 and 48 h). Of these, 98% were ME/CFS-specific, compared with the two healthy controls accompanying the longitudinal study. Principal component analysis illustrated the three distinct clusters at the 0 h, 24 h, and 48 h timepoints, but with heterogeneity among the patients within the clusters, highlighting dynamic methylation responses to exertion in individual patients. There were 24 ME/CFS-specific DMFs at gene promoter fragments that revealed distinct patterns of temporal methylation across the timepoints. Functional enrichment of ME-specific DMFs revealed pathways involved in endothelial function, morphogenesis, inflammation, and immune regulation. These findings uncovered temporally dynamic epigenetic changes in stress/immune functions in ME/CFS during PEM and suggest molecular signatures with potential for diagnosis and of mechanistic significance.
dc.description.confidentialfalse
dc.edition.editionSeptember 2025
dc.identifier.citationSharma S, Hodges LD, Peppercorn K, Davis J, Edgar CD, Rodger EJ, Chatterjee A, Tate WP. (2025). Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise. International Journal of Molecular Sciences. 26. 17.
dc.identifier.doi10.3390/ijms26178563
dc.identifier.eissn1422-0067
dc.identifier.elements-typejournal-article
dc.identifier.issn1661-6596
dc.identifier.number8563
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/73642
dc.languageEnglish
dc.publisherMDPI (Basel, Switzerland)
dc.publisher.urihttps://www.mdpi.com/1422-0067/26/17/8563
dc.relation.isPartOfInternational Journal of Molecular Sciences
dc.rights(c) 2025 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectME/CFS
dc.subjectCPET
dc.subjectepigenetics
dc.subjectDNA methylation
dc.subjectpost-exertional malaise
dc.titlePrecision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise
dc.typeJournal article
pubs.elements-id503395
pubs.organisational-groupOther
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