The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective of this review was to synthesize qualitative and quantitative data from research examining the gut microbiota composition, inflammatory markers, and therapeutic outcomes of interventions targeting the microbiome in the context of ME/CFS.

Methods: The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS. This comprehensive search utilized databases such as PubMed, Scopus, and Web of Science, with keywords including “ME/CFS,” “Gut-Brain Axis,” “Gut Health,” “Intestinal Dysbiosis,” “Microbiome Dysbiosis,” “Pathophysiology,” and “Therapeutic Approaches.” Where possible, insights from clinical trials and observational studies were included to enrich the findings. A narrative synthesis method was also employed to effectively organize and present these findings.

Results: The study found notable changes in the gut microbiota diversity and composition in ME/CFS patients, contributing to systemic inflammation and worsening cognitive and physical impairments. As a result, various microbiome interventions like probiotics, prebiotics, specific diets, supplements, fecal microbiota transplantation, pharmacological interventions, improved sleep, and moderate exercise training are potential therapeutic strategies that merit further exploration.

Conclusions: Interventions focusing on the gut-brain axis may help reduce neuropsychiatric symptoms in ME/CFS by utilizing the benefits of the microbiome. Therefore, identifying beneficial microbiome elements and incorporating their assessments into clinical practice can enhance patient care through personalized treatments. Due to the complexity of ME/CFS, which involves genetic, environmental, and microbial factors, a multidisciplinary approach is also necessary. Since current research lacks comprehensive insights into how gut health might aid ME/CFS treatment, standardized diagnostics and longitudinal studies could foster innovative therapies, potentially improving quality of life and symptom management for those affected.

Source: Hsu CY, Ahmad I, Maya RW, Abass MA, Gupta J, Singh A, Joshi KK, Premkumar J, Sahoo S, Khosravi M. The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review. J Transl Med. 2025 May 11;23(1):530. doi: 10.1186/s12967-025-06527-x. PMID: 40350437. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06527-x (Full text)

Research Supports the Integration of Acupuncture in Mainstream Health Care for the Management of Chronic Diseases

Abstract:

Purpose: To address the role of acupuncture in mainstream health care for symptom relief, condition outcome, pain management, and shared therapy in resolving chronic diseases. This article explores how acupuncture education can adapt to meet the standards required for inclusion in conventional health care.

Objectives: To discuss the future of acupuncture education and its part in training providers for inclusion in a comprehensive health care system that involves physician acupuncturists and licensed acupuncturists for treating and managing specific chronic diseases. To strategize the future of acupuncture education at an advanced clinical level that fosters incorporating acupuncture therapy into selected allopathic settings. To encourage the recognition of translational research for promoting the acceptance of acupuncture by providers and insurers.

Conclusion: Translational research employs clinical evidence to support acupuncture therapy when incorporated into selected areas of allopathic practices, including pain management, palliative care for patients with end-stage cancer, sleep disorders, anxiety disorders, post-traumatic stress, female hormonal conditions such as premenstrual syndrome and menopausal syndrome, as well as chronic fatigue syndromes including Myalgic encephalomyeltitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Advanced clinical training in acupuncture schools and postgraduate certification courses are required to prepare acupuncturists to safely and effectively provide the specialized integrative acupuncture services needed in these clinical areas.

Source: Williams JE, Kim Y, Moramarco J. Research Supports the Integration of Acupuncture in Mainstream Health Care for the Management of Chronic Diseases. Med Acupunct. 2025 Apr 17;37(2):106-111. doi: 10.1089/acu.2024.0108. PMID: 40308724; PMCID: PMC12038303. https://pubmed.ncbi.nlm.nih.gov/40308724/

Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological adverse effect after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations. However, clinicians do not recognize the condition well, and no case report has shown a full recovery.

Case presentation: We present a 65-year-old Japanese female who experienced severe fatigue, postexertional malaise, orthostatic intolerance, and various symptoms after her third SARS-CoV-2 vaccination. Following thorough examinations and excluding other potential diagnoses, she met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The symptoms persisted for 30 months and improved ultimately with comprehensive treatment and a self-management strategy, including pacing management, pharmacological treatments, and psychiatric interventions to support those struggling with the despair over the devastating symptoms.

Conclusion: This case report describes ME/CFS following the SARS-CoV-2 vaccination and its full recovery. It illustrates the importance of considering the differential diagnosis of psychiatric disorders and addressing the condition through psychiatric interventions. Our findings provide new insights into treating ME/CFS and the vaccination-related adverse effects.

Source: Kurotori I, Sasao W, Abe M. Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report. PCN Rep. 2025 Apr 27;4(2):e70111. doi: 10.1002/pcn5.70111. PMID: 40291166; PMCID: PMC12034265. https://pmc.ncbi.nlm.nih.gov/articles/PMC12034265/ (Full text)

Dietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systematic Review

Abstract:

Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmunological disorder with limited treatment options. Despite the widespread use of Dietary Supplements (DSs) among ME/CFS patients to alleviate fatigue and associated symptoms, evidence remains inconclusive. This systematic review aims to provide an updated synthesis of the efficacy of DS interventions and explore possible mechanisms underlying their therapeutic effects.

Methods: This systematic review was conducted according to PRISMA guidelines. Several databases (Ebsco Host, PubMed, Scopus, Google Scholar) were used for the systematic search, which was based on the broad search terms ME/CFS and DS with a focus on publications between 1994 and 2024. The primary outcome was fatigue, with additional considerations including psychological well-being, physical activity, and biochemical markers. Two independent researchers screened the studies for eligibility in a multi-stage process and assessed quality and bias using Cochrane’s risk of bias tools (RoB-2, ROBINS-I).

Results: Fourteen studies (N = 809) of heterogeneous designs were included, showing a high risk of bias, mostly due to missing data and selection bias. While some interventions (L-carnitine and guanidinoacetic acid, oxaloacetate, CoQ10-selenium combination, NADH and NADH-CoQ10 combination) showed significant reductions in fatigue, methodological limitations, like small sample sizes and missing data, prevent firm conclusions. Mixed results were reported for secondary outcomes like cognitive function and inflammatory markers. Six studies noted adverse effects, including nausea and insomnia.

Conclusions: Though some DSs showed potential in reducing fatigue in ME/CFS, methodological limitations and inconsistent results hinder definitive conclusions. Future research should improve diagnostic criteria and include more diverse populations.

Source: Dorczok MC, Mittmann G, Mossaheb N, Schrank B, Bartova L, Neumann M, Steiner-Hofbauer V. Dietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systematic Review. Nutrients. 2025 Jan 28;17(3):475. doi: 10.3390/nu17030475. PMID: 39940333; PMCID: PMC11819863. https://pmc.ncbi.nlm.nih.gov/articles/PMC11819863/ (Full text)

Effect of Immunoadsorption on clinical presentation and immune alterations in COVID-19-induced and/or aggravated ME/CFS

Abstract:

Autoreactive antibodies (AAB) are currently being investigated as causative or aggravating factors during post-COVID. In this study we analyze the effect of immunoadsorption therapy on symptom improvement and the relationship with immunological parameters in post-COVID patients exhibiting symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) induced or aggravated by an SARS-CoV-2 infection. This observational study includes 12 post-COVID patients exhibiting a predominance of ME/CFS symptoms alongside increased concentrations of autonomic nervous system receptors (ANSR) autoantibodies and neurological impairments.

We found that following immunoadsorption therapy, the ANSR autoantibodies were nearly eliminated from the patients’ blood. The removal of IgG antibodies was accompanied by a decrease of pro-inflammatory cytokines including IL4, IL2, IL1β, TNF and IL17A serum levels, and a significant reduction of soluble spike protein. Notably, a strong positive correlation between pro-inflammatory cytokines and ASNR-AABs β1, β2, M3, and M4 was observed in spike protein-positive patients, whereas no such correlation was evident in spike protein-negative patients.

30 days post-immunoadsorption therapy, patients exhibited notable improvement in neuropsychological function and a modest but statistically significant amelioration of hand grip strength was observed. However, neither self-reported symptoms nor scores on ME/CFS questionnaires showed a significant improvement and a rebound of the removed proteins occurring within a month.

Source: Anft M, Wiemers L, Rosiewicz KS, Doevelaar A, Skrzypczyk S, Kurek J, Kaliszczyk S, Seidel M, Stervbo U, Seibert FS, Westhoff TH, Babel N. Effect of Immunoadsorption on clinical presentation and immune alterations in COVID-19-induced and/or aggravated ME/CFS. Mol Ther. 2025 Jan 9:S1525-0016(25)00011-5. doi: 10.1016/j.ymthe.2025.01.007. Epub ahead of print. PMID: 39797400. https://www.cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(25)00011-5.pdf (Full text) https://pubmed.ncbi.nlm.nih.gov/39797400/ (Abstract)

The effects of 3-month supplementation with synbiotic on patient-reported outcomes, exercise tolerance, and brain and muscle metabolism in adult patients with post-COVID-19 chronic fatigue syndrome (STOP-FATIGUE): a randomized Placebo-controlled clinical trial

Abstract:

Purpose: Considering the observed gastrointestinal issues linked to post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), beneficially modulating the gut microbiota could offer a safe, cost-effective nutritional strategy. This trial aimed to evaluate the effects of medium-term synbiotic supplementation on patient-reported outcomes, exercise tolerance, and tissue metabolism in patients with post-COVID-19 ME/CFS.

Methods: Between September 2022 and December 2023, we investigated the impact of 3-month supplementation with a synbiotic mixture including L. rhamnosus DSM 32550, Humiome® L. plantarum DSM 34532, B. lactis DSM 32269, B. longum DSM 32946, fructooligosaccharides and zinc, on predetermined primary and secondary outcome measures in twenty six post-COVID-19 ME/CFS patients utilizing a parallel-group, randomized, placebo-controlled, double-blind design.

Results: Both the synbiotic and placebo intake resulted in a significant reduction in general fatigue after 3 months compared to the baseline values (P ≤ 0.05). This was accompanied by a significant interaction effect (time vs. treatment) for post-exercise malaise (P = 0.02), with synbiotic superior to placebo to attenuate post-exercise malaise. The synbiotic also demonstrated a significant advantage over placebo in increasing choline levels at the thalamus (P = 0.02), and creatine levels at left frontal white matter (P = 0.05) and left frontal grey matter (P = 0.04).

Conclusion: Taking the synbiotic mixture for three months improves tissue metabolism and mitigates clinical features of post-COVID-19 fatigue syndrome. The presented data show promise in addressing the widespread issue of ME/CFS following the COVID-19 pandemic; however, further validation is needed before endorsing the synbiotics within this clinical context. The study is registered at ClinicalTrials.gov (NCT06013072).

Source: Ranisavljev M, Stajer V, Todorovic N, Ostojic J, Cvejic JH, Steinert RE, Ostojic SM. The effects of 3-month supplementation with synbiotic on patient-reported outcomes, exercise tolerance, and brain and muscle metabolism in adult patients with post-COVID-19 chronic fatigue syndrome (STOP-FATIGUE): a randomized Placebo-controlled clinical trial. Eur J Nutr. 2024 Nov 26;64(1):28. doi: 10.1007/s00394-024-03546-0. PMID: 39592468. https://pubmed.ncbi.nlm.nih.gov/39592468/

A Case Report of Chronic Epipharyngitis With Chronic Fatigue Treated With Epipharyngeal Abrasive Therapy (EAT)

Abstract:

A case of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with chronic epipharyngitis was treated with epipharyngeal abrasive therapy (EAT). The symptoms of ME/CFS improved along with the improvement of chronic epipharyngitis. The patient was followed up with endocrine and autonomic function tests.

Endocrine function tests included salivary cortisol and salivary α-amylase activity. Salivary α-amylase activity was stimulated by EAT. EAT improved the diurnal variability of salivary cortisol secretion. Autonomic function tests included heart rate variability analysis by orthostatic stress test. EAT normalized parasympathetic and sympathetic reflexes over time and regulated autonomic balance.

Based on the improvement of symptoms and test results, EAT was considered effective for ME/CFS. A literature review was conducted on the mechanism of the therapeutic effect of EAT on ME/CFS.

Source: Hirobumi I. A Case Report of Chronic Epipharyngitis With Chronic Fatigue Treated With Epipharyngeal Abrasive Therapy (EAT). Cureus. 2024 Feb 23;16(2):e54742. doi: 10.7759/cureus.54742. PMID: 38405656; PMCID: PMC10884883. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884883/ (Full text)

The impact of “long COVID” on menstruation in Chinese female college students and the intervention of acupuncture

Abstract:

This study aimed to explore the potential application value of acupuncture in alleviating the impact of long COVID on women’s menstrual cycles, by investigating the occurrence of long COVID among female college students, its effects on menstruation, and the intervention of acupuncture. This cross-sectional study surveyed female college students with a history of coronavirus disease 2019 (COVID-19) before April 10, 2023.

A questionnaire was used to analyze demographic characteristics, post-COVID sequelaes, duration of symptoms, and treatments received during that period. Among the 731 participants enrolled in the survey, 468 were female undergraduate students who met the analysis criteria. Among them, 85 individuals fit the definition of “Long COVID” (18.16%).

Within the group of patients with long COVID, 69 individuals experienced changes in their overall menstrual patterns compared to the 6 months prior to contracting the novel coronavirus (81.18%). Additionally, 17 individuals opted for acupuncture treatment following the onset of COVID-19 (20.00%), which resulted in less impact on their menstrual cycle (41.18% vs 64.71% without receiving acupuncture, OR = 2.62), menstrual period duration (41.18% vs 64.71%, OR = 2.62), menstrual flow (47.06% vs 69.18%, OR = 2.52), and the color of menstrual blood (41.18% vs 63.24%, OR = 2.46) among these patients. Long COVID had a certain impact on menstruation.

Acupuncture potentially alleviates the clinical symptoms of long COVID and reduces its impact on women’s menstrual cycle, thus having potential therapeutic value in the treatment of long COVID.

Source: Dong J, Ni J, Zhang Z, Yan H, Xu J, Zhao J. The impact of “long COVID” on menstruation in Chinese female college students and the intervention of acupuncture. Medicine (Baltimore). 2024 Feb 9;103(6):e36818. doi: 10.1097/MD.0000000000036818. PMID: 38335408; PMCID: PMC10860984. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860984/ (Full text)

Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

Abstract:

Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as long COVID.
The effects of long COVID can be far-reaching, with a duration of up to six months and a range of symptoms such as cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive dysfunction, and thrombus formation. However, recent studies have shown that naringenin and naringin have palliative effects on various COVID-19 sequelae. Flavonoids such as naringin and naringenin, commonly found in fruits and vegetables, have various positive effects, including reducing inflammation, preventing viral infections, and providing antioxidants.
This article discusses the molecular mechanisms and clinical effects of naringin and naringenin on treating the above diseases. It proposes them as potential drugs for the treatment of long COVID, and it can be inferred that naringin and naringenin exhibit potential as extended long COVID medications, in the future likely serving as nutraceuticals or clinical supplements for the comprehensive alleviation of the various manifestations of COVID-19 complications.
Source: Liu S, Zhong M, Wu H, Su W, Wang Y, Li P. Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature. Microorganisms. 2024; 12(2):332. https://doi.org/10.3390/microorganisms12020332 https://www.mdpi.com/2076-2607/12/2/332 (Full text)

Improving Quality of Life in Chronic Fatigue Syndrome using Antioxidant Complex Twendee M®.

Abstract:

Chronic fatigue syndrome (CFS) is a disease in which fatigue that interferes with daily life persists for six months or longer. The number of patients with CFS is increasing, as CFS-like symptoms have been reported to occur in the sequelae of both COVID-19 infection and the SARS-CoV-2 vaccine, both of which have become significant issues in recent years. While the pathogenesis mechanism is not yet fully understood, research suggests that oxidative stress (OS) may play a role in the development of CFS.
In this paper, we discuss the antioxidant potential of the antioxidant formulation Twendee M® (TwM) and the results of a questionnaire that monitored changes in symptoms before and after TwM in a total of 23 men and women diagnosed with CFS. TwM is a supplement containing 15 different ingredients, and has a strong antioxidant capacity that cannot be achieved with a single antioxidant ingredient.
The results of the questionnaire showed that TwM significantly improved all of the major symptoms of CFS, including fatigue, muscle pain, joint pain, sleep disturbance, decreased memory and concentration, and headache. TwM was shown to alleviate various symptoms of CFS and improve quality of life.
Source: You, F.; Harakawa, Y.; Yoshikawa, T.; Inufusa, H. Improving Quality of Life in Chronic Fatigue Syndrome using Antioxidant Complex Twendee M®.. Preprints 2024, 2024020373. https://doi.org/10.20944/preprints202402.0373.v1 https://www.preprints.org/manuscript/202402.0373/v1 (Full study available as PDF file)