Chronic fatigue syndrome is characterized by dizziness, sleep problems, chronic pain and fatigue. For years, clinicians debated about whether chronic fatigue syndrome was actually a condition, because it is so difficult to diagnose, and there are no biomarkers for the illness. Eventually, the problems that patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) were recognized. And now, researchers are beginning to understand the physiological problems that underlie ME/CFS. These findings, which have revealed complex links between metabolism, the gut microbiome, and immunity, may also benefit long COVID patients, who often have symptoms that are similar to those of ME/CFS.
In this study, which was reported in Nature Medicine, researchers used computational tools to analyze data from lab tests that were performed on samples from 249 individuals.
“Our study achieved 90% accuracy in distinguishing individuals with chronic fatigue syndrome, which is significant because doctors currently lack reliable biomarkers for diagnosis,” said study author Dr. Derya Unutmaz, Professor in immunology at The Jackson Laboratory (JAX). “Some physicians doubt it as a real disease due to the absence of clear laboratory markers, sometimes attributing it to psychological factors.”
This study combined an analysis of clinical symptoms and omics technologies to find novel ME/CFS biomarkers. Since the disorder is so variable from one patient to another, it was crucial to connect symptoms to biological data. Variations in the gut microbiome, metabolites, immune factors, and clinical symptoms like headache, sleep problems, and dizziness were considered together. The researchers developed a novel computational tool to leverage all of this data, from 153 patients and 96 unaffected individuals over four years.
The work showed that immune cell data could predict symptom severity; and gut microbiome data provided insights into gut, mood, and sleep problems. Patients who were affected for four years or fewer carried networks that were less disrupted compared to those who had been ill for over a decade.
In unaffected individuals, the interactions and links between gut microbiome, metabolites, and the immune system reflected a healthy balance. But in ME/CFS patients, there was significant disruption and disorder in patients with sleep disorders, pain, fatigue, and mood disturbances.
The study also revealed that in ME/CFS patients, there are comparatively low levels of butyrate, a short-chain fatty acid generated by the gut microbiome that is known to be associated with good health. Imbalances in the gut microbiome were also reflected by higher than usual levels of benzoate, tryptophan, and other biochemicals. Immune responses were also heightened, especially those relating to MAIT cells, which are sensitive to the health of the gut microbiome.
“MAIT cells bridge gut health to broader immune functions, and their disruption alongside butyrate and tryptophan pathways, normally anti-inflammatory, suggests a profound imbalance,” said Unutmaz. “Our data indicate these biological disruptions become more entrenched over time. That doesn’t mean longer-duration ME/CFS can't be reversed, but it may be more challenging.”
ME/CFS often arises after a viral infection, like long COVID.
While more research will be needed with more affected individuals to confirm these findings, they also provide a good starting point for many more investigations that could find the causes of ME/CFS, and potentially, how to treat it and similar disorders.
Sources: Jackson Laboratory, Nature Medicine