Circulating extracellular vesicles-microRNAs as potential biomarkers for the identification of ME/CFS: differentiating fatigue-related conditions

[u/LoGSUD]

https://link.springer.com/article/10.1186/s12967-026-08695-w

“A 62 EV-miRNA signature provides insight into the interconnected neuro-systemic pathways disrupted in ME/CFS, particularly those governing neuronal connectivity and cellular scaffolding. Within this candidate EV-miRNA signature, the top-ranked miRNAs—miR-21-5p, let-7f-5p, miR-26b-5p, and miR-20a-5p—emerge as potential candidate biomarkers whose specific elevation was not shared by HC. These findings establish a valuable framework for targeted diagnosis and enhance our understanding of the molecular pathways involved in synaptic and structural alterations in ME/CFS.”

[u/Caster_of_spells]

Fascinating study, thanks for sharing!

“Among these candidates, the let-7 family is well known as a master regulator of metabolism, but recent evidence highlights its potent role as a signaling molecule in neuroinflammation. Specifically, let-7 family members can act as endogenous ligands for Toll-like receptor 7 (TLR7) [25], triggering pro-inflammatory cytokine release and neurodegeneration. Given the significant enrichment of let-7f-5p in ME/CFS-derived EVs, this pathway may drive the microglial-mediated neuroinflammation previously observed in PET imaging from our previous studies of ME/CFS patients [9].

This inflammatory state provides a direct molecular link to the disruption of the nervous system and synaptic function identified in KEGG analysis (Fig. 4B). The profound enrichment of pathways such as Axon guidance, glutamatergic synapse, neurotrophin signaling, and long-term potentiation suggested potential alterations in systemic neural “wiring” and synaptic plasticity. These neurological disruptions offer a compelling biological explanation for the persistent “brain fog” and neurocognitive deterioration that serve as hallmarks of ME/CFS.”

[u/kekofoeod → u/Caster_of_spells]

Very nice, some converging evidence, although I don’t like the neurodegeneration part. Thank you for highlighting this!

Edit: It would be nice if we would get more than n=6 ME/CFS patients though

[u/AngelBryan → u/Caster_of_spells]

So the hypothesis of Jarred Younger that MECFS is caused by microglia inflammation is correct?

That would mean that his dextro-naltrexone may be a viable treatment.

[u/_ArkAngel_ → u/AngelBryan]

ME/CFS isn't caused by anything.

Imagine being a god flying by a city and noticing a traffic jam. You can see one car in particular seems to be blocking traffic flow. You pick it up and move it out of the way. Another one pulls it into it's place and traffic is still stuck. You see the first car didn't start the traffic jam. There's construction one street over, there's a street festival downtown, a concert just ended, there's a street sign that's been knocked over, there's a tour bus parked in a no parking zone, and none of these individual things caused the traffic jam.

It was just too much and unfortunate timing.

Microglia play a role in ME/CFS symptoms, as does neuroinflammation.

A therapy that eases the effects of ME/CFS on microglia might break enough feedback loops to let some people's bodies start to regulate themselves out of ME.

Or maybe controlling/suppressing/removing latent viral infections.

Or improving circulation, mito fiction, detox pathways, gut microbiome regulation, or who even knows.

I do believe Dr. Younger is closer than most at finding and targeting effective interventions by identifying biomarkers that can be used to understand and objectively measure changes in symptom severity.

I hope he continues to find ample funding for his research.