Evidence browser

Gut MicrobiomeEnergy MetabolismInterventionsImmune System

Gut microbiome-immune-metabolic axis in fatigue: mechanistic insights and food science approaches.

Kim, Joonbeom, Son, Bokyung, Yoo, Woongjae et al.·Food science and biotechnology·2026

This review examined research linking gut bacteria and their products to fatigue in several conditions, including ME/CFS and long COVID. Researchers observed that people with fatigue-related conditions often show alterations in their gut microbiome—for example, reduced production of beneficial short-chain fatty acids and signs of a leaky gut barrier. The review suggests that certain foods (fiber, fermented products, prebiotics, and polyphenols) may support recovery through microbiome pathways, but notes that more controlled studies are needed before drawing firm conclusions.

Gut MicrobiomeAutonomic Nervous SystemDiagnosticsImmune System

Association between myalgic encephalomyelitis/chronic fatigue syndrome and irritable bowel syndrome: a systematic review and meta-analysis.

Rajabi, Natalie, Ramdass, Prakash V A K·Frontiers in medicine·2026

A new systematic review combined data from 22 studies to examine how often irritable bowel syndrome (IBS) and ME/CFS occur together. Researchers reported that people with ME/CFS were substantially more likely to also have IBS compared to people without ME/CFS, and that about 37% of people with ME/CFS in these studies had IBS. However, the results varied considerably depending on which diagnostic criteria were used to define ME/CFS, suggesting uncertainty about the true overlap.

NeuroinflammationEnergy MetabolismImmune SystemCognitive Impairment

Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.

Jin, Hongjiao, An, Yi, Huang, Jingwei et al.·Frontiers in immunology·2026

This systematic review proposes a framework for understanding post-exertional malaise (PEM)—the worsening of symptoms after mild activity—by examining how energy production, immune activation, and brain inflammation may be associated with each other in people with Long COVID and chronic fatigue conditions. The authors suggest that in vulnerable individuals, exercise may trigger an abnormal cascade involving damaged mitochondria (cellular energy factories), inflammatory molecules, and changes in how the brain perceives fatigue and pain. However, this is a theoretical model based on existing literature; individual mechanisms have not been directly tested in a single study.

E0 ConsensusReviewPEM not requiredMeta-Analysis

Risks of autoimmune and inflammatory post-acute COVID-19 conditions: a network cohort study in six European countries, the USA and Korea.

Burkard, Theresa Ms, López-Güell, Kim, Català, Martí et al.·BMJ public health·2026

This large study looked at whether people who had COVID-19 were more likely to develop autoimmune or inflammatory conditions—including ME/CFS and POTS—in the 9 months after infection. Researchers examined health records from over 2.5 million people across eight countries and did not observe increased rates of these conditions in COVID-19 patients compared to people who tested negative. However, the findings do not yet tell us whether similar patterns apply to ME/CFS specifically, and the study was observational rather than experimental.

Autonomic Nervous SystemImmune SystemLong COVID Overlap

E0 ConsensusReviewPEM requiredEditorial

Myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia - overlap, differences, and emerging insights.

Murovska, Modra, Krumina, Angelika, Araja, Diana et al.·Journal of translational medicine·2026

ME/CFS and fibromyalgia are two different but often overlapping illnesses that cause severe fatigue, pain, and other debilitating symptoms. While they share many similarities, ME/CFS has a distinctive feature called post-exertional malaise—where activity makes symptoms dramatically worse for hours or days—while fibromyalgia does not. This review shows that the two conditions have different immune system patterns and may require different treatment approaches.

Severe MEImmune SystemCognitive ImpairmentPost-Exertional Malaise

BiomarkersGut MicrobiomeEnergy MetabolismImmune System

Biomarkers of post-acute infection syndrome: a systematic literature review.

Wendt, Katharina, Schieck, Maximilian, Gille, Christian et al.·Frontiers in immunology·2026

This systematic review examined laboratory findings and molecular markers across 142 studies of post-acute infection syndromes, including post-COVID and ME/CFS. Researchers observed that energy metabolism, immune signalling, and gut bacteria appear to be altered in these conditions, with a central control pathway called NF-κB potentially linking many of these changes. However, the studies reviewed used very different methods and tested different molecules, so no single marker has yet been confirmed as reliable for diagnosis or treatment.

NeuroinflammationPain and SensitizationImmune SystemLong COVID Overlap

A systematic scoping review and conceptual analysis of new-onset fibromyalgia manifestations after non-hospitalized COVID-19: empirics, definitions, methodologies, pathophysiology, mapping of literature, and knowledge gaps.

Plaut, Shiloh·Journal of translational medicine·2026

This systematic review examined published studies on fibromyalgia-like symptoms that develop after mild COVID-19 infection. Researchers searched medical databases and found 228 studies reporting overlap between long COVID, chronic fatigue, and fibromyalgia, but noted that different studies use inconsistent definitions and methods, making it difficult to draw firm conclusions. The causes of these overlapping conditions remain unclear.

BiomarkersInterventionsSleepImmune System

Therapeutic plasma exchange and immunomodulatory strategies in post-infectious syndromes: A review of immune dysregulation in PTLDS, long COVID, ME/CFS, and PANS/PANDAS.

Kaplan, Gary·Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis·2026

This review examines whether immune system abnormalities in ME/CFS, long COVID, and related post-infectious conditions might respond to immune-modifying treatments such as plasma exchange and immunoglobulin therapy. The authors report that while some patients with specific immune markers showed improvements in observational studies, two large controlled trials (RituxME in ME/CFS and a TPE trial in long COVID) did not demonstrate benefit in unselected patient groups, suggesting that better ways to identify which patients might benefit are needed.

NeuroinflammationPain and SensitizationBiomarkersImmune System

Clinical applications of epigenetic signatures in chronic pain management and health outcome prediction.

Ben Amar, Jinane, Michiels, Joni, Hendrix, Jolien et al.·Epigenomics·2026

This review examined how epigenetic changes—chemical switches that turn genes on and off without altering DNA itself—are observed in chronic pain conditions including fibromyalgia and ME/CFS. Researchers found that alterations in DNA methylation and other epigenetic marks are associated with inflammation, pain signaling, and sensitization pathways. The review suggests that epigenetic markers may one day help identify people at risk or predict outcomes, though these applications remain preliminary and require further development.

E0 ConsensusReviewPEM requiredReview-Narrative

Gut Microbiome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Insights into Disease Mechanisms.

Nikolova, Ralitsa, Donchev, Deyan, Vaseva, Katya et al.·International journal of molecular sciences·2025

This review examines the connection between gut bacteria and ME/CFS, a condition characterized by exhaustion that worsens after activity. The authors explain how an imbalance in gut bacteria may damage the intestinal barrier, allowing bacterial particles to enter the bloodstream and trigger inflammation throughout the body. They also discuss how changes in gut bacteria might affect the brain, contributing to the brain fog and cognitive problems many ME/CFS patients experience.

Gut MicrobiomeImmune SystemPost-Exertional Malaise

E0 ConsensusReviewPEM not requiredReview-Narrative

A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome.

Morse, Brinkley A, Motovilov, Katherine, Michael Brode, W et al.·Brain, behavior, and immunity·2025

This review examines intravenous immunoglobulin (IVIG), a treatment that works by providing immune-boosting antibodies, for several conditions including ME/CFS and long COVID. The researchers found that IVIG may help reduce symptoms in some patients, though results have been mixed. The treatment can have side effects and is very expensive, which limits how widely it can be used.

E0 ConsensusReviewPEM requiredReview-Narrative

Biomarkers over Time: From Visual Contrast Sensitivity to Transcriptomics in Differentiating Chronic Inflammatory Response Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Dooley, Ming·International journal of molecular sciences·2025

This review examines how doctors can better distinguish between two similar-looking illnesses: Chronic Inflammatory Response Syndrome (CIRS) and ME/CFS. The authors trace how testing methods have evolved from simple vision tests to advanced blood tests that read genetic activity. They suggest that some patients diagnosed with ME/CFS may actually have CIRS, which is treatable if properly identified.

BiomarkersImmune System

Insights into the Complex Biological Network Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Dudova, Dobrina, Bozhkova, Martina, Petrov, Steliyan et al.·International journal of molecular sciences·2025

This review brings together research showing that ME/CFS involves multiple body systems going wrong at the same time—including problems with the immune system, energy production in cells, hormone balance, and gut health. These problems appear to feed into each other, creating a cycle that keeps the illness going. The findings suggest ME/CFS is not just one thing breaking down, but rather many interconnected systems all struggling together.

NeuroinflammationEnergy MetabolismImmune SystemPost-Exertional Malaise

NeuroinflammationImmune System

Cognitive Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Aetiology and Potential Treatments.

Bansal, Amolak Singh, Seton, Katharine A, Brooks, Jonathan C W et al.·International journal of molecular sciences·2025

Many ME/CFS patients experience brain fog and difficulty concentrating, which can be as disabling as physical symptoms. This review examined how ongoing low-level inflammation and viral activity in the body may damage thinking and memory by affecting blood flow and nerve function in the brain. The researchers suggest that treating inflammation, controlling viral reactivation, and improving how cells produce energy could potentially help restore cognitive function.

E0 ConsensusReviewPEM not requiredReview-Narrative

From tradition to healing: the promise of acupuncture in managing chronic fatigue syndrome.

Wang, Delong, Yang, Tiansong, Cui, Yang et al.·Frontiers in medicine·2025

This article reviews what we know about ME/CFS and explores how acupuncture—a traditional Chinese medicine practice—might help treat it. The authors summarize research on what causes ME/CFS, how doctors diagnose it, and discuss both historical and modern approaches to using acupuncture and related techniques to manage symptoms.

NeuroinflammationBiomarkersImmune System

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): diagnosis and management.

Fan, Jin, Jiao, Jiao, Chang, Hai-Qing et al.·Journal of translational medicine·2025

This comprehensive review examines how ME/CFS is diagnosed and treated based on current medical knowledge. The authors found that ME/CFS is caused by problems with the immune system, energy production in cells, and brain inflammation, but there are currently no definitive blood tests to confirm the disease. Treatment options include both medication approaches (targeting immune dysfunction and cell energy) and non-medication strategies like activity pacing and cognitive behavioral therapy, though doctors now recognize that exercise programs can actually harm some patients.

E0 ConsensusReviewPEM unclearMeta-Analysis

Endometriosis and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis.

Compton, Sabrina, Alkabalan, Rodolf, Cadet, Judd et al.·Diagnostics (Basel, Switzerland)·2025

This research found that women with endometriosis (a painful condition affecting the uterus) are nearly three times more likely to develop ME/CFS than women without endometriosis. Both conditions involve similar patterns of immune system problems and ongoing inflammation. The study combined results from multiple research papers to show this connection is real and consistent across different groups of patients.

E0 ConsensusReviewPEM requiredSystematic-Review

Applicability and adaptation of cognitive behavior therapy for long COVID neuropsychiatric symptoms: a review with insights from ME/CFS.

Takamatsu, Naoki, Kuga, Hironori·BMC infectious diseases·2025

This review examined whether cognitive behavior therapy (CBT)—a talking therapy that helps address thought patterns and behaviors—might help patients with long COVID who experience brain fog, fatigue, and mood problems. The authors compared long COVID to ME/CFS, noting they share many features, and found that while CBT may help some patients feel less tired and think more clearly, it works best when tailored to each person's energy limits and combined with other treatments. Importantly, the authors stress that suggesting CBT does not mean these illnesses are 'all in your head'—they have real physical causes.

NeuroinflammationImmune SystemPost-Exertional Malaise

Gulf War Illness, Fibromyalgia, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Overlap in Common Symptoms and Underlying Biological Mechanisms: Implications for Future Therapeutic Strategies.

Mantle, David, Domingo, Joan Carles, Golomb, Beatrice Alexandra et al.·International journal of molecular sciences·2025

This review examines four conditions—Gulf War Illness, fibromyalgia, ME/CFS, and long COVID—that share similar symptoms like fatigue, pain, and brain fog. Researchers found that these disorders may share common biological problems, particularly with how cells produce energy (mitochondria), manage stress, and control inflammation. The authors suggest that a supplement called CoQ10 might help because it supports cellular energy production and reduces harmful inflammation.