Exercise interventions for physical function, psychological health, and quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and network meta-analysis.

Persistent fatigue in long-COVID is not associated with peripheral inflammatory or cellular stress biomarkers: A cross-sectional controlled study.

Chronic overlapping pain conditions (COPCs) affect young adults and pose significant challenges in medical care. This study aimed to describe the types and number of current and past medical providers and medications used by young adults with COPCs and to explore associations between health care utilization, clinical pain, and psychosocial factors. Fifty young adults (mean age: 27.16y) with COPCs were recruited and completed online questionnaires assessing demographics, pain intensity and interference, number of pain conditions, health care providers consulted, medication use, and psychosocial characteristics. Relationships among health care utilization, clinical pain measures, and psychosocial variables were analyzed using Pearson correlations and linear regression models. Participants reported an average of 4.40 COPCs, with fibromyalgia, chronic low back pain, and chronic fatigue syndrome being the most common. Most (72%) were currently receiving medical treatment, with primary care physicians being the most frequently consulted providers. The average number of current providers was 2.82, while the number of past providers was 4.28. Despite extensive health care engagement, 77.7% reported no improvement or worsening of their condition. No significant associations were found between the number of providers or medications and clinical or psychosocial outcomes. The findings highlight gaps in the effectiveness of health care utilization for young adults with COPCs. The high prevalence of provider visits and medication use without substantial symptom improvement suggests a need for more integrated, multidisciplinary care approaches. Future research should focus on optimizing treatment strategies and identifying opportunities for early intervention.

Long-term follow-up data on the travel-associated burden of vector-borne diseases (VBDs) are scarce. A prospective multi-site observational study was conducted to delineate the longitudinal course, symptom patterns, physical and mental burden and factors associated with prolonged illness in travellers after four VBDs. Patients with confirmed travel-associated acute chikungunya, dengue, Zika or falciparum malaria were recruited at 15 GeoSentinel sites from 2016 to 2021. Persistent signs and symptoms were evaluated at 1, 3, 6, 12 and 18months (M) post-diagnosis, using a multi-modular study questionnaire with quality of life (QOL) evaluated by 12-item short-form health survey (SF-12). Demographic, premorbid and acute disease characteristics were tested in multivariate analyses to determine factors associated with persistence of symptoms at M3. Missing data were imputed by rules and statistical methods. Among 273 patients enrolled, 35 (13%) had chikungunya, 110 (40%) dengue, 19 (7%) Zika and 109 (40%) falciparum malaria. Median age was 38years (interquartile range 30-49), 148/273 (54%) were men. At M3, 24/35 (69%) of chikungunya, 27/110 (25%) of dengue, 8/19 (42%) of Zika and 12/109 (11%) of malaria patients had persistent symptoms. The proportion of symptomatic chikungunya patients was 18/35 (51%) at M6, mainly due to musculoskeletal symptoms including arthritis and stiffness. In dengue patients, fatigue and musculoskeletal symptoms without arthritis persisted until 1year. Zika patients reported persisting headaches, musculoskeletal symptoms including arthritis and fatigue. One month after malaria, fatigue was the main persisting symptom, which resolved almost completely at M3. At M12, 6/35 (17%) of chikungunya, 5/110 (5%) dengue, 3/19 (16%) Zika and only 1/109 (1%) of malaria patients were still symptomatic.Impaired QOL was noted at M3 by 23/35 (66%) of patients with chikungunya, 20/110 (18%) with dengue and 6/19 (32%) with Zika but only 4/109 (4%) with malaria. Female sex, Zika, chikungunya and musculoskeletal symptoms during acute infection were associated with persistent M3 symptoms. Post-arboviral symptoms and impaired QOL persisted beyond 6months after chikungunya, dengue and Zika. In contrast, post-malaria fatigue syndrome resolved within 3months.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness marked by fatigue, cognitive impairment, and post-exertional malaise. Gastrointestinal (GI) symptoms are frequently reported, yet their relationship to central features of the illness and biological correlates remains poorly understood. We aimed to characterize GI symptom burden in ME/CFS and evaluate its associations with core clinical features and specific immune and inflammatory markers, with attention to potential gut-related contributions to disease expression. GI symptoms and 49 additional symptoms across nine domains were assessed in 116 ME/CFS patients and 80 matched controls. Plasma C-reactive protein (CRP) and antibodies against dietary and microbial antigens were measured as indicators of systemic inflammation and putative gut-derived antigen exposure. ME/CFS patients reported significantly elevated GI symptom frequency and severity compared with controls, with 53% of ME/CFS patients versus 8% of controls reporting a prior diagnosis of irritable bowel syndrome. GI symptom burden correlated with fatigue, cognitive difficulties, flu-like symptoms, pain, sleep disturbances, neurological complaints, and sensory sensitivities, independent of illness duration. CRP levels were higher in patients with greater GI symptoms and correlated with GI, fatigue, musculoskeletal pain, and flu-like symptom burden. Patients with greater flu-like symptom expression exhibited higher IgM responses to dietary gliadin and bacterial lipopolysaccharide. These associations were not detected in controls. GI symptoms are a prominent, clinically relevant dimension of ME/CFS, associated with broader symptom burden and inflammatory heterogeneity. These findings highlight the relevance of gut-related and immune processes in ME/CFS and underscore the value of incorporating GI symptom assessment in translational studies to help refine mechanistic understanding and improve therapeutic stratification.

ABSTRACT Background Various chronic health conditions are associated with household vulnerability to food insecurity. There is limited evidence regarding the prevalence of food insecurity or the experiences and challenges related to nutrition and food access among people living with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long Covid (LC) in Aotearoa New Zealand. Methods Adults were recruited between June and September 2025 from online communities, support networks and primary care providers to complete an anonymous, online survey. Food insecurity was defined as ‘sometimes’ or ‘never’ being able to afford to eat properly, or ‘sometimes’ or ‘always’ having food run out, eating less, eating less variety due to cost, relying on others for food or using food grants/banks. Descriptive results were reported as percentages; multivariable risk ratios were estimated from generalised linear models. Quotes from open-ended questions were used to illustrate the quantitative findings. Results Among 333 respondents, half (50%) had experienced food insecurity in the past 12 months. There was an inverse-J shape association between food insecurity and disease severity. Younger respondents were more likely to face food insecurity than older respondents. Beyond financial constraints, reported challenges to adequate nutrition included physical limitations affecting going shopping, receiving online deliveries and preparing meals. Conclusion Findings support the need to recognise ME/CFS and LC as disabilities for the purposes of social service and income support provision, which could relieve some of the financial pressures on patients. We also recommend that GPs routinely screen for food insecurity among people with ME/CFS or LC.

Long COVID is a prevalent condition characterised by pain, fatigue, disability, and a multitude of health issues. There are various treatment options for managing long COVID symptoms, including non-pharmacological interventions like physiotherapy and rehabilitation, which can be effectively delivered either in institutional care settings or via telerehabilitation. This three-arm randomised controlled trial included 145 participants selected from a population-based cohort in eight administrative divisions in Bangladesh. Participants aged 18 and above diagnosed with chronic fatigue syndrome(CFS) secondary to long COVID were included and history of fatigue, cardiovascular, neuro-musculoskeletal, or respiratory diseases, or red flag signs were excluded. Participants were allocated to three groups: hospital-based rehabilitation (HBR), telerehabilitation (TR), or a home programme (HP). Interventions consisted of an individualised exercise programme. The HBR and TR groups received physiotherapist-supervised sessions with sessions lasting 45min, twiceweekly for 8 weeks. And the HP group performed exercises independently following structured instruction. Fatigue, the primary outcome, was measured using the Chalder fatigue scale, while secondary outcomes were quality of life measured using the 36-item Short Form Survey (SF-36), disability-adjusted life years (DALYs), and cardiorespiratory parameters (blood pressure, pulse rate, oxygen saturation, and lung capacity). Between 1st July 2023 and 31st December 2023, 145 participants were enrolled, with a mean age of 46.1 ± 6.7years. After 8weeks of intervention, the among-group within-group comparison showed a significant difference in fatigue level (HBR: P < 0.001; TR: P < 0.001; HP: P < 0.321), physical functioning (HBR: P < 0.001; TR: P < 0.001; HP: P < 0.057), and episodic disability (HBR; TR; HP: P < 0.001) among the participants when comparing them between the groups. In multiple comparisons, results showed that differences were observed in the Chalder fatigue scale, physical functioning, and episodic disability between all groups. Hospital-based rehabilitation showed a lower mean score compared to telerehabilitation (p < 0.0001) and the home programme (p < 0.0001). Additionally, telerehabilitation was significantly better than the home programme (p < 0.0001), indicating hospital-based rehabilitation's superior efficacy in reducing fatigue, improving physical function, and reducing disability. Physiotherapy as hands-on implementation in a hospital setting was substantially more effective than telerehabilitation. Training healthcare professionals to improve accessibility to rehabilitation would help mitigate the consequences of long COVID-19. The trial was registered with the clinical trial registry of India (CTRI/2023/03/050808. Registered on 17/03/2023).

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, disabling condition with limited evidence-based treatment options. Self-management support is recommended to improve people's coping and quality of life, yet little is known about whether the provided self-management support meet individuals with ME/CFS and their next of kins needs. The aim of this study was to explore the self-management support needs of individuals with ME/CFS and their next of kin, and to identify barriers and facilitators to effective self-management support in order to inform improvements to existing self-management interventions. We conducted an exploratory descriptive qualitative study using a combination of semi-structured individual and focus group interviews with a total of 16 participants (12 individuals with ME/CFS and four next of kin) in Norway. Data were analysed thematically within a constructivist framework. We identified three main themes. Theme one was named "Individualised and accessible support", focusing on the importance of timing, readiness, and flexible delivery formats (digital, hybrid, modular). The second theme was named "Continuity and validation", emphasising current gaps in follow-up care for individuals with ME/CFS and experiences of stigma. The third main theme was named "The role of peer support and practical strategies", highlighting the value of peer interaction, sharing experiences, and adaptive tools (e.g., pacing, symptom tracking). Overall, the participants described that existing self‑management support was poorly aligned with their physical and cognitive limitations, lacked consistent and structured follow‑up, and often conveyed contradictory guidance on activity management. Self-management support for individuals with ME/CFS should be integrated into standardised care pathways, delivered in phased and modular formats, and include structured follow-up. Digital and hybrid solutions can enhance accessibility. Including peer-led components and family involvement may foster empowerment and reduce isolation. Training healthcare professionals in ME-sensitive communication and developing national guidelines are critical to improving service quality and reducing stigma.

BackgroundPost-COVID condition (PCC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) show marked clinical overlap, suggesting a shared post-infectious pathophysiology. This study aims to characterize the longitudinal change of autonomic function, small-fiber integrity, cognitive performance, and clinical symptoms in PCC and ME/CFS, and to determine whether trajectories differ between diagnostic groups.MethodsThirty-eight participants (21 PCC, 17 ME/CFS) underwent two standardized evaluations separated by a median of 31 months. Assessments included comprehensive autonomic testing, small-fiber evaluation, and an extensive neuropsychological battery.ResultsME/CFS showed longer disease duration than PCC at baseline (median 42 vs. 12 months), while the interval between evaluations was comparable (31 vs. 30 months). Baseline profiles were largely overlapping, although ME/CFS showed nominally higher QST warm detection thresholds (p = 0.034), greater autonomic symptom burden (p = 0.038), and lower hemodynamic scores (p = 0.019), none surviving FDR correction. Cross-domain analyses linked small-fiber symptoms with autonomic symptom burden (Rho = 0.65, pFDR = 0.002) and fatigue (Rho = 0.55, pFDR = 0.018), while fatigue was negatively associated with processing speed (Rho = − 0.57, pFDR = 0.004), attention (Rho = − 0.49, pFDR = 0.018), and executive function (Rho = − 0.44, pFDR = 0.047). Rank-transformed mixed-effects models identified FDR-corrected Time effects, with increases in CHEPs (pFDR < 0.001) and verbal memory (pFDR = 0.010), and decreases in processing speed (pFDR = 0.006) and QST cold thresholds (pFDR = 0.038).ConclusionsPCC and ME/CFS showed broadly overlapping multidomain profiles, with particularly similar profiles at follow-up. This suggests that, among individuals with persistent symptoms, PCC may increasingly resemble longer-standing ME/CFS across autonomic, small-fiber/sensory, and cognitive domains. These findings are consistent with overlapping post-infectious mechanisms, but do not establish identical disease trajectories or definitive disease convergence.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-026-08321-9.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is adebilitating multisystem disorder characterized by profound fatigue, post-exertional malaise (PEM), immune dysregulation, and mitochondrial dysfunction. While radiation exposure has been linked to fatigue syndromes with overlapping pathophysiology, no previous reports have described the effects of therapeutic radiation, including proton beam radiotherapy (PBRT), in patients with ME/CFS. We report the case of a46-year-old woman with apre-existing, clinically confirmed diagnosis of ME/CFS (Bell score60, ECOG1), who underwent postoperative PBRT (50.4 Gy in 28fractions) for arecurrent left sphenoid wing meningioma (CNS WHO grade1). The tumor had been surgically resected but showed residual disease with early postoperative progression and close proximity to the left optic nerve, prompting the indication for adjuvant radiotherapy. The patient initially tolerated treatment well, with only mild acute worsening of pre-existing fatigue and transient corticosteroid-responsive symptoms. However, within weeks of completing radiotherapy, she developed progressive and severe worsening of fatigue, myalgia, vertigo, and hypersensitivity to sensory stimuli as well as cognitive decline. Over several months, she became completely bedridden (Bell score0, ECOG4) with persistent ME/CFS aggravation unresponsive to supportive measures persisting until the last known contact 20months after radiation. Follow-up imaging showed stable postoperative findings without tumor progression or new structural brain lesions. This case illustrates aprofound and irreversible deterioration of ME/CFS following PBRT, suggesting that radiation-induced mitochondrial dysfunction, oxidative stress, and chronic inflammatory activation may critically worsen pre-existing metabolic fragility. Despite the theoretical advantages of proton radiotherapy in reducing normal tissue exposure, its protective effects may be insufficient in patients with baseline mitochondrial malfunction. This is, to our knowledge, the first reported case of severe and sustained ME/CFS exacerbation after radiotherapy. The case emphasizes the urgent need for risk stratification, tailored consent processes, and research in the field of radiotherapy tolerance in ME/CFS patients, as conventional expectations regarding side effects may not predict outcomes in this vulnerable population.

Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) share overlapping symptoms, and emerging evidence implicates persistent fibrinoid microclots in their pathophysiology, contributing to impaired microcirculation. This review explores the role of microclots and evaluates thromboelastography (TEG) as a potential diagnostic tool. A comprehensive literature review was conducted using major biomedical databases. Studies indicate microclots are prevalent in both conditions. Long COVID patients demonstrate a TEG profile of increased clot strength (maximum amplitude) and reduced fibrinolysis (LY30), suggesting a persistent hypercoagulable state. Despite its advantages in real-time assessment, TEG interpretation faces challenges from preanalytical variability and a lack of standardized protocols. Promising therapeutic trials, including anticoagulants (e.g., apixaban) and fibrinolytics (e.g., lumbrokinase), require further validation. Technological advancements like AI-driven TEG analysis and portable devices could improve diagnostic precision. In conclusion, persistent microclots are a key pathophysiological feature. TEG provides a promising, novel approach for detecting coagulation abnormalities and could guide treatment, but requires standardization in future clinical trials. Future research should integrate multiomics biomarkers for precision therapeutics to improve patient outcomes.

Large language models can synthesize biomedical knowledge, parse vast amounts of data, and generate code, positioning them as promising tools for biomarker discovery from high-throughput omics data. Here, we benchmark six models from OpenAI, Anthropic, and Google on plasma cell-free RNA datasets spanning three clinical cohorts: Kawasaki disease versus multisystem inflammatory syndrome in children, active tuberculosis versus symptomatic respiratory controls, and myalgic encephalomyelitis/chronic fatigue syndrome versus sedentary controls. We evaluate literature-guided nomination of diagnostic gene panels for downstream machine learning and autonomous construction of end-to-end classifiers from raw count matrices to held-out test predictions. Despite prompt adherence issues, model-nominated panels recapitulate canonical immune pathways and outperform random panels across cohorts, even matching differential gene expression baselines in the tuberculosis cohort. End-to-end automation proves feasible but is model- and task-dependent. One model approaches conventional performance for Kawasaki disease versus multisystem inflammatory syndrome in children, whereas performance decreases for tuberculosis and myalgic encephalomyelitis/chronic fatigue syndrome cohorts. These findings delineate current capabilities and limitations of large language models in diagnostics and open a path for their future use in biomarker discovery.

Study on Sijunzi decoction regulating intestinal microbiota structure and metabolic profile for improving chronic fatigue syndrome.

UHPLC-Q-Exactive Orbitrap MS-based brain-gut metabolomics implicates multi-pathway modulation by Ginseng stem-leaf saponins in chronic fatigue syndrome mice.

Q-fever can cause long-term health complications such as Q-fever Fatigue Syndrome (QFS), which may severely impact patients' Health-Related Quality of Life (HRQoL). This study investigated change of HRQoL in QFS patients over time, and explored predictors associated with change using longitudinal data. In this prospective observational study questionnaires were administered among Dutch individuals with self-reported QFS who were registered at Q-support, a foundation that supports, advises and informs Q-fever patients. Participants completed four annual questionnaires between 2021 and 2024, including EQ-5D-5L and EQ VAS to measure HRQoL. Changes in HRQoL were categorized as "improvement", "deterioration", or "stable", using an anchor-based minimal important difference approach. Multinomial logistic regression analyses identified predictors of change. A total of 199 patients were included in the final analysis. At baseline, median EQ-5D-5L utility index and EQ VAS scores were 0.647 (IQR: 0.352-0.774), and 50.0 (IQR: 34.0-60.0), respectively. After four years, 37% of patients showed improvement in EQ-5D-5L utility, 30% deterioration, and 33% remained stable. Female sex and higher baseline EQ-5D-5L utility were associated with lower odds of improvement or being stable. More than 10 years post-infection, HRQoL remains consistently low at group level among patients with QFS, with substantial long-term variability in individual outcomes. These findings underscore the chronic nature of QFS, its long-lasting consequences, and the importance of continued monitoring of individual health trajectories. Further studies are warranted to better understand the mechanisms underlying individual differences in recovery and to inform targeted interventions for this patient population.

This cross-sectional study, conducted January 15-June 30, 2025 at Jilin Province FAW General Hospital, assessed the knowledge, attitudes, and practices (KAP) of postoperative patients regarding postoperative fatigue syndrome (POFS), a multifactorial condition characterized by persistent fatigue, reduced energy, and functional impairment following surgery that cannot be relieved by rest. Among 310 valid responses, knowledge scored a median of 3 out of 20, while attitude and practice medians were 36/45 and 32/45 respectively. Multivariate linear regression identified knowledge (β = 0.348, 95% CI 0.225-0.470, P < 0.001), attitude (β = 0.491, 95% CI 0.350-0.632, P < 0.001), monthly per capita household income of 5,000-20,000 yuan (β = 2.485, 95% CI 1.210-5.107, P = 0.013), and presence of POFS (β = 1.831, 95% CI 0.684-2.979, P = 0.002) as independent factors associated with practice scores. Structural equation modeling suggested potential direct effects of knowledge (β = 0.290, P = 0.009) and attitude (β = 0.361, P = 0.003) on practice. The findings suggest overall poor POFS knowledge, relatively positive attitudes, and suboptimal self-management practices, underscoring the need for targeted patient education to improve recovery outcomes and reduce systemic healthcare burden.

Children, adolescents, and young adults (CYP) with postacute infection and vaccination syndromes (PAIVS), and/or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), experience profound loss in activity and participation. We introduce and psychometrically validate two new brief, age-adapted, and domain-specific questionnaires for clinical use assessing activity and participation in this vulnerable patient group. For this, 91 patients (aged 10-25 years) were assessed at the Munich Chronic Fatigue Center (MCFC) from 12/2022 to 11/2024. We designed the MCFC Activity Scale and MCFC Participation Scale and assessed construct validity using confirmatory factor analysis for both questionnaires. Reliability was evaluated via Cronbach's α. Factor-based MCFC Activity and Participation Scores (0-100) were derived and correlated with Bell Score, FSS, DSQ-PEM, and SF-12 Component Summary Scales (PCS and MCS). Discrimination for ME/CFS was evaluated using ROC analyses. Participants (mean age 15.6 ± 2.4 years) were predominantly female (64%). 65% were diagnosed with ME/CFS. The MCFC Activity Scale showed excellent one-factor fit (comparative fit index, CFI = 1.00) and good internal consistency (α = 0.82). The MCFC Participation Scale showed good internal consistency (α = 0.85) and acceptable one-factor fit (CFI = 0.817). Factor-based activity and participation were strongly correlated yet distinct (r = 0.73). DerivedMCFC Activity and Participation Scores differed significantly by ME/CFS diagnosis (p ≤ 0.009). Scores correlated with Bell Score, FSS, DSQ-PEM, and SF-12 PCS (all p ≤ .002). For ME/CFS discrimination, the Activity Score achieved an AUC = 0.78 and the Participation Score an AUC = 0.72.Conclusion: The Activity Scale demonstrated strong construct validity. The Participation Scale showed good internal consistency. Both scores demonstrated good convergent validity with established patient-reported outcome measures, supporting clinical utility. They may serve as pragmatic screening tools for this vulnerable patient group.

Hyperbaric oxygen therapy (HBOT) has been proposed as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but evidence remains limited. This study evaluated its clinical effectiveness and feasibility, as well as associated functional brain changes. Thirty patients with ME/CFS (mean age 42.3 ± 11.7 years; 7 males, 23 females) received 40 HBOT sessions. Clinical outcomes were assessed at baseline, during treatment, and four weeks post-treatment. The primary outcome was change in the physical functioning subscale of the Short Form-36 Health Survey (SF-36 PF). Secondary outcomes included severity of core symptoms assessed via questionnaires, exercise capacity, handgrip strength, cognitive performance, orthostatic intolerance, and brain magnetic resonance imaging (MRI; volumetry and functional connectivity [FC]). Thirty age- and sex-matched healthy controls (mean age 42.3 ± 11.3 years; 7 males, 23 females) were included for MRI comparison. SF-36 PF significantly improved during HBOT compared with baseline (g = 0.71, p = 0.006). SF-36 pain (p = 0.002, g = 0.79) and Chalder Fatigue Scale also showed clinically meaningful reductions (p < 0.001, g = -0.87). Exercise capacity (g = 0.66), muscle strength (g = 0.40), and information processing speed (g = 0.52) improved significantly after treatment (all p < 0.05). Treatment adherence was high and tolerability was favorable, with no major adverse events reported. Functional MRI analyses revealed increased thalamic FC in ME/CFS patients compared to healthy controls in bilateral sensorimotor (p < 0.001, t = 5.65, FDR-corrected) and visuo-occipital regions (p < 0.001, t = 5.40, FDR-corrected) at baseline. Following HBOT, thalamic hyperconnectivity shifted toward patterns observed in healthy controls. Responders, defined as a ≥ 10 points increase in SF-36 PF, showed greater reductions in thalamic hyperconnectivity than non-responders (p < 0.001, t = -4.34 to -5.18, FDR-corrected). HBOT was well tolerated and associated with significant improvements in physical functioning, fatigue, pain, and cognitive performance in ME/CFS. The post-treatment shift in thalamocortical connectivity toward healthy control patterns and its association with clinical response support the hypothesis that functional thalamic dysregulation contributes to ME/CFS pathophysiology and may be modulated by HBOT. This provides a network-level rationale for controlled trials to confirm therapeutic efficacy. ClinicalTrials.gov NCT06118138. Registered 01 November 2023 - Retrospectively registered, https://clinicaltrials.gov/study/NCT06118138?cond=ME%2FCFSamp;term=HBOTamp;rank=1 .

ABSTRACT Background People living with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often use pacing with a heart-rate monitor (HRM) to manage their activity intensities to minimise time spent over their anaerobic threshold; however, there is little research related to their experiences of this approach. Objective To explore the experiences of people with ME/CFS of pacing with an HRM. Methods 488 people with ME/CFS completed an online international survey, and 27 agreed to online follow-up semi-structured interviews. The open answers from the survey and the data from the interviews were analysed using reflective thematic analysis. Results 87% of the survey participants and 88% of the interviewees were female. 49% of the survey participants and 44% of the interviewees were between 35 and 50 years. Their ME/CFS severity ranged from mild to severe. Some themes matched the questions: Benefits, Negatives, Support and Ideal Design, and some themes emerged from the data: Barriers, Body awareness/Intuition, Acceptance and Recommendations. Conclusions This study produced further insights into pacing with an HRM not previously published related to benefits, ideal design and support. New themes were also identified: Body awareness/Intuition, Barriers, Acceptance and Recommendations. The majority of people with ME/CFS in this study felt that pacing with an HRM is a useful management tool, but randomised controlled trials are needed to determine who benefits and identify guidelines to minimise the negatives and reduce the barriers for people with ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease with unknown biological basis and no cure. Microbiome dysbiosis has been reported in people with ME/CFS but its relevance to pathophysiology is unknown. Gut microbes are an important source of tryptophan metabolites that activate the aryl hydrocarbon receptor (AHR), a regulator of homeostatic and inflammatory genes. Dysregulated activation of AHR contributes to pathophysiology of several neuroimmune and chronic diseases but its role in ME/CFS has not been investigated. The purpose of this study was to investigate the production of tryptophan metabolites and AHR agonists by gut microbes of people with ME/CFS. We found lower diversity and altered microbiome community structure in people with ME/CFS and changes in the subcommunity of microbes that correlated with tryptophan metabolites. Using targeted metabolomics we identified nine metabolites elevated in the stool of people with ME/CFS, including three AHR agonists. Stool ex vivo cultures were tested for their capacity to activate AHR in a reporter cell line and by qPCR. AHR activation did not differ between people with ME/CFS and controls, however, we detected elevated agonist activity in people with neurocognitive symptoms, regardless of underlying disease. These findings are consistent with previous work revealing changes in the gut microbiome of people with ME/CFS and adds further support to alterations in tryptophan metabolism associated with the disease. Altered AHR activity by gut microbial metabolites may be a common mechanism contributing to neurocognitive symptoms in diseases including ME/CFS.