The Biological Basis of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome

The disabling illness described as either Chronic Fatigue Syndrome (CFS) or Myalgic Encephalomyelitis (ME) results in a wide spectrum of symptoms, the most disabling often being a profound lack of energy, muscle pain, headache, and cognitive issues.  The illness is also characterized by an increase in symptoms when in the upright position or following physical activity that would not be challenging to a healthy individual (post-exertional malaise).  The factors that incite and perpetuate the illness are unknown, few treatment options exist, and full recovery is rare.  We have previously investigated the possibility that a member of the murine retrovirus family could be involved.   While that virus has been eliminated as a suspect, the existence of one or more inciting pathogens has not been ruled out.  Well-documented outbreaks of ME/CFS implicate an infectious cause for at least some cases.  Rapid onset following a viral illness has been reported, though many individuals recount a more gradual onset with no clear single provocation.

Project: Extracellular Vesicles in ME/CFS

Cells signal each other through release and uptake of cytokines and extracellular vesicles (EVs). The three types of EVs are exosomes, produced through exocytosis, microvesicles, which bud from the cell membrane, and apoptotic bodies, which are products of dying cells. EVs carry both proteins such as cytokines and microRNAs, which can influence gene expression and activity of recipient cells. We are isolating EVs from ME/CFS patients and healthy controls and examining their protein, metabolite, and RNA cargo.

This project is funded through our NIH ME/CFS Center and more information can be found on the Center website:
https://neuroimmune.cornell.edu/research/vesicles-and-signaling/

Project: Mitochondria and ME/CFS

Dysfunction of mitochondria, the energy-generating organelle in human cells, is one hypothesis concerning the severe fatigue experienced by ME/CFS patients. To investigate whether there are genetic differences in the mitochondrial DNA of patients and healthy controls, we have sequenced the mitochondrial genome of a cohort of subjects recruited by the Chronic Fatigue Initiative.

A publication for this project was published in the Journal of Translational Medicine:
Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome.
by Paul Billing-Ross, Arnaud Germain, Kaixiong Ye, Alon Keinan, Zhenglong Gu, and Maureen R. Hanson
J. Translational Medicine. 2016, 14:19

Click here for a simplified explanation of the JTM publication.

We are currently investigating the properties of mitochondria in white blood cells of patients and controls.

Project: Post-Exertional Malaise in ME/CFS


In collaboration with Dr. Betsy Keller in the School of Health Sciences and Human Performance at Ithaca College, we are examining the physiological and molecular basis of the exercise intolerance characteristics of CFS/ME patients. We are examining the effect of a maximal exercise stress test on gene expression, metabolism, inflammatory markers, and cytokine levels in ME/CFS patients and healthy controls.

Project: Transcriptomes of Immune Cells in ME/CFS

The activity of circulating leukocytes have been reported by various past studies to differ between ME/CFS patients and controls, possibly resulting from infectious agents, autoimmunity, or immune system disturbances. Using subjects selected by Dr. Susan Levine (Manhattan, NY), Dr. Rita Shaknovich’s lab (previously at Weill Cornell Medical School) purified B, T, and NK cells for preparation of mRNAs, from which cDNA libraries were prepared for Illumina sequencing libraries at the Cornell Sequencing Facility. These are being analyzed by Dr. Fabien Campagne and by Olivier Elemento’s group at Weill Cornell Medical School. MicroRNAs from the three cell types are being analyzed in collaboration with Dr. Andrew Grimson (Dept. of Molecular Biology and Genetics).

Completed Project: The Microbiome and ME/CFS

Many individuals with ME/CFS describe digestive disturbances. These symptoms might result from altered composition of the gut microbiome, as is known in intestinal inflammatory diseases. We have characterized the gut bacterial and eukaryotic microbiome in a cohort of ME/CFS patients vs. healthy controls, using 16S rRNA sequencing and 18S rRNA sequencing, respectively. We have observed a greater bacterial diversity in the ME/CFS patients and have observed differences in the taxonomic composition of the microbiomes of individuals and of the two populations.

Results of the study are available here:

Hanson MR and Giloteaux L. 2017.  The gut microbiome in Myalgic Encephalomyelitis.  The Biochemist  39 (2): 10-13.

Giloteaux L, Goodrich JK, Walters WA, Levine SM, Ley RE, Hanson MR. 2016.  Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome.  Microbiome 4(1):30.

Giloteaux, L, Hanson MR, Keller, BA. 2016. A pair of identical twins discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome differ in physiological parameters and gut microbiome composition  American Journal Case Reports 17:720-729

Mandarano AH, Giloteaux L, Keller BA, Levine SM, Hanson MR.  2018. Eukaryotes in the gut microbiota in myalgic encephalomyelitis/chronic fatigue syndrome. PeerJ 6:e4282.

Project Sponsors

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