In this 129th edition of the Research Digest, we highlight emerging research that continues to deepen understanding of ME/CFS and long COVID as complex, multisystem conditions. This month’s articles explore the potential role of the gut microbiome in immune, inflammatory and neurological symptoms, as well as altered brain connectivity linked to cognitive fatigue and brain fog. We also include a personal account that powerfully reflects the lived experience of ME/CFS and the often-hidden cost of trying to function while managing a complex chronic illness.
Contributing Digesters: Lauren, Sarah & Simone.
Please note: The Research Digest shares current scientific findings for awareness and discussion. It is not a substitute for medical advice or treatment guidance, as much of the research featured is in its early stages and requires further confirmation.
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REVIEW
Gut microbiome and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Insights into disease mechanisms
Authors: Nikolova R, Donchev D, Vaseva K, Ivanov IN (National Center of Infectious and Parasitic Diseases, Bulgaria)
Publication: International Journal of Molecular Sciences (December, 2025)
Link: https://www.mdpi.com/1422-0067/27/1/425
Easy Read Overview: This review found that people with ME/CFS often have changes in their gut microbiome, including lower levels of beneficial bacteria and higher levels of some bacteria linked to inflammation. These changes may weaken the gut barrier and contribute to immune system problems, inflammation, and symptoms affecting the brain and nervous system. However, it is still unclear whether these microbiome changes cause ME/CFS or are a result of the illness, and more research is needed.
This narrative review examined evidence linking gut microbiome alterations with ME/CFS disease mechanisms and symptom development. The authors aimed to summarise current microbiome findings in ME/CFS and explore how gut dysbiosis may contribute to immune dysfunction, inflammation, and neurological symptoms.
The authors searched PubMed, Scopus, Web of Science, and Google Scholar using terms related to gut microbiota, dysbiosis, the gut-brain axis, and ME/CFS. No date restrictions were applied. Included studies used several diagnostic criteria, including Fukuda, Canadian Consensus Criteria (CCC), International Consensus Criteria, and Institute of Medicine (IOM) criteria. Reviewed microbiome studies ranged from small cohort studies to large genome-wide association analyses.
Across studies, ME/CFS patients commonly showed reduced microbial diversity and altered bacterial composition compared with healthy controls. Several studies identified lower levels of anti-inflammatory, butyrate-producing bacteria, including Faecalibacterium, Bifidobacterium, Roseburia, and Eubacterium rectale. Increased levels of potentially pro-inflammatory bacteria, including Alistipes and Clostridium bolteae, were also reported.
The authors discussed evidence that reduced butyrate production may weaken intestinal barrier integrity, allowing bacterial products such as lipopolysaccharides (LPS) to enter the bloodstream and promote chronic low-grade inflammation. Dysbiosis may also influence neurocognitive symptoms through the microbiota–gut–brain axis, altered neurotransmitter signalling, and disrupted tryptophan metabolism.
The authors suggest microbiome changes may contribute to symptom severity and immune dysfunction in ME/CFS, although it remains unclear whether dysbiosis is a cause or consequence of the illness. They emphasise the need for larger, standardised longitudinal studies and note that microbiome-targeted therapies, including probiotics, dietary interventions, and faecal microbiota transplantation, remain experimental but potentially promising.
BIOLOGY
Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study
Author: Inderyas M, Thapaliya K, Marshall-Gradisnik S, & Barnden L (Griffith University, Australia)
Publication: Journal of Translational Medicine (January 2026)
Link: https://link.springer.com/article/10.1186/s12967-026-07708-y
Easy Read Overview: This study looked at brain scans from people with ME/CFS, long COVID, and healthy controls before and after a challenging thinking task. It found that people with ME/CFS and long COVID had changes in how different parts of the brain communicated with each other, and these changes were linked to the severity of cognitive symptoms such as brain fog and mental fatigue. The findings suggest that altered brain connectivity may contribute to cognitive problems in both conditions and could help researchers develop future biomarkers for symptom severity.
Patients with ME/CFS and long COVID frequently report symptoms of neurocognitive deficits and cognitive fatigue. Functional connectivity (FC), the correlation of activity between different brain regions, is able to provide some indication of how brain networks coordinate during activities and at rest. The authors investigated intrinsic FC correlates of cognitive fatigue amongst ME/CFS and long COVID patients.
This was a cross-sectional study involving 78 participants.. This included 32 people with ME/CFS (pwME/CFS, Canadian Consensus Criteria and/or International Consensus Criteria), 19 people with long COVID (pwLC, Delphi Consensus), and 27 healthy controls (HC). Functional and structural MRI data was collected from all participants, with readings taken pre (to measure baseline) and post (to measure fatigue) completion of a cognitively challenging task (the Stroop paradigm). Questionnaires captured demographics, quality of life, and symptom inventories.
Compared with the HC group, pwME/CFS and pwLC exhibited altered FC within subcortical and core brain networks. The pwLC group was characterised by reduced connectivity between the nucleus accumbens and vermis, and increased connectivity between the prefrontal cortex and hippocampus, while pwME/CFS showed increased connectivity between the cuneiform nucleus and medulla and abnormalities within core networks. Connectivity involving the cerebellum, amygdala, caudate, red nucleus, and hippocampus was associated with cognitive symptom severity in both conditions. In addition, hippocampal and cerebellar connectivity were related to illness duration in ME/CFS.
The authors conclude that these findings indicate that reduced hippocampal–nucleus accumbens connectivity may be associated with impaired motivation and cognition. Compared with HCs, pwME/CFS and pwLC showed altered functional connectivity across key brain networks, suggesting reduced and dysregulated neural coordination. These changes may represent potential biomarkers of symptom severity in both conditions.
MEDIA
I kept crashing after the school run and taking time off work. Then doctors said three words.
Authors: Cashman M
Publication: Mamamia
Link: https://www.mamamia.com.au/navigating-chronic-fatigue/
In this article, Melissa Cashman describes her experience of developing with ME/CFS. Of ME/CFS, she wrote:
• It makes you doubt your own thoughts and question your own body.
• It makes people tell you to try “going for a walk” a lot. A lot.
• It makes you say, “Sorry baby, Mummy is too tired to play” when you desperately want to.
• It makes you explain what CFS actually is. Constantly.
• It makes you see ‘the face’ all the time – the ‘are you sure?’ or ‘doesn’t sound real’ face.
Melissa also wrote that, “The hardest part is that from the outside, you can still look mostly normal. People see you answering emails, picking up your kids, and assume you’re okay.
They don’t see the crash afterwards. They don’t see what it costs.”
