“While what gives rise to ME/CFS remains obscure, understanding the ways it disrupts the body's various biological processes on the molecular level is revealing biomarkers for specific ME/CFS subtypes that may inform clinical research and lead to targeted interventions”
W. Ian Lipkin, MD, News Medical
News Medical, an online publication, have reported on a new paper produced by a research team at Colombia University and published in Nature (3rd September 2025), titled, ‘Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.' Dr Charles Shepherd, MEA Hon. Medical Adviser, has provided comment and summary of the key takeaways from the research below.
Extracts: News Medical – Research reveals molecular details of ME/CFS and long COVID
As part of the new study, researchers analyzed blood samples from 56 ME/CFS patients and 52 healthy controls recruited in New York and California. They used molecular testing to map the metabolome (metabolites of cellular metabolism) and proteome (proteins produced through biological processes). They also examined immune responses to microbial stimulation – a simulated infection – before and after exercise.
In ME/CFS patients, they observed disruptions in interconnected pathological processes that are often observed in chronic inflammatory conditions, suggesting a state of metabolic dysfunction, immune dysregulation, and tissue damage, potentially triggering a systemic inflammatory response. Understanding these relationships is crucial for developing therapeutic strategies targeting multiple aspects of the disease process.
- Impaired cellular energy production, which may lead to physical and mental exhaustion and the accumulation of toxic metabolites.
- Lipid abnormalities that contribute to tissue damage and perpetuate inflammation.
- Disruptions to the extracellular matrix which provides structural support and regulates cell behavior and release of signaling molecules that promote inflammation.
- Disruption of epithelial barriers, particularly in the gut which can contribute to the development of gut dysbiosis, where the balance of gut microbiota is altered resulting in the translocation of bacterial products into the blood where they trigger inflammation.
- Activation of the complement system of the innate immune system, the overactivation of which can contribute to tissue damage, inflammation, and sustained fatigue.
- Disturbances in copper-dependent antioxidant pathways, which can promote oxidative stress, promote inflammation, and contribute to tissue injury.
- Dysregulation of tryptophan-serotonin-kynurenine pathways, which can lead to impaired cognitive function.
MEA Comment
New research on immune system and metabolic dysfunction in ME/CFS
This is a useful new piece of research from America in that it helps to confirm what we already know, or suspect, about the way in which ME/CFS develops following an infection.
In other words:
- Some people have a genetic predisposition to developing ME/CFS after an infection, especially a viral infection, or some other form or immune system stressor
- The immune system fails to return to normal, possibly through continuing low level activation, after the initial response to the infection
- Persisting low level immune system activation could in turn lead to low level inflammation in various parts of the body
- The abnormal and persisting immune system response results in various disturbances to the way in which the body creates energy at a cellular level – affecting both physical and mental performance, manages temperature control and regulates the autonomic nervous system
In addition, and based on some of these laboratory based findings, the researchers suggest a number of treatments that may be worth assessing in clinical trials. These include carnitine (a muscle energy supplement), metformin (which is normally used to treat type 2 diabetes), 5 hydroxytryptophan (a naturally occurring amino acid that is converted into serotonin) and pre or probiotics (to improve the gut microbiome).
I am, however, concerned about the possible use of drugs called SSRIs which raise the level of a brain chemical transmitter called serotonin. I have a lot of patient feedback and personal experience on the use of these antidepressant drugs (examples include Lustral and Prozac) and it is clear that some people with ME/CFS are very sensitive and react quite badly even at lower than normal doses.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
Further media coverage
- EurekAlert | Sept 1, 2025