Tag: gastrointestinal complaints

Gastrointestinal symptoms correlate with core clinical features and systemic inflammation in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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. https://link.springer.com/article/10.1186/s12967-026-08442-1 (Full text available as PDF file)

Symptom clusters in ME/CFS reflect distinct neuroimmune and autonomic pathophysiological mechanisms: a translational model

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disease characterized by heterogeneous symptom patterns. Previous work suggested that specific symptoms tend to co‑occur, pointing toward underlying biological mechanisms. This study aimed to empirically validate literature‑based, hypothesis‑driven symptom clusters and assess whether they reflect distinct neuroimmune and autonomic pathophysiological pathways.

Methods: Symptom data from 748 adults with ME/CFS (≥20 years) participating in the APAV‑ME/CFS study were analyzed. Symptoms were assigned to predefined mechanistic groups informed by current pathophysiological hypotheses. Exploratory and Confirmatory Factor Analyses, followed by Structural Equation Modeling (SEM), evaluated the coherence, distinctiveness, and hierarchical structure of each cluster. Robustness was tested using a stratified, randomized training dataset.

Results: A coherent Brain factor (brain fog, sensory hypersensitivity, visual disturbances, sleep disturbances, headaches) showed excellent fit (RMSEA = 0.021; CFI = 0.996). Gastrointestinal symptoms demonstrated stronger internal consistency than Immune symptoms, and model comparisons supported a two‑factor Gut–Immune structure. Across all analyses, symptom groups emerged as internally consistent and statistically distinct. A higher‑order SEM including a common latent factor yielded excellent fit for the Autonomic symptom complex.

Conclusions: The findings support ME/CFS as a complex neuroimmune–autonomic multisystem disorder and suggest that symptom clusters align with functional biological systems. Mechanism-aligned symptom subgrouping may enable pathophysiology-guided diagnostics, patient stratification, and targeted therapeutic development. The proposed interpretations of underlying mechanisms derive from the integration of existing literature and were not directly measured in this study. The identified clusters therefore indicate mechanistic alignment rather than direct mechanistic validation.

Source: Habermann-Horstmeier L, Horstmeier LM. Symptom clusters in ME/CFS reflect distinct neuroimmune and autonomic pathophysiological mechanisms: a translational model. J Transl Med. 2026 Apr 28;24(1):606. doi: 10.1186/s12967-026-08159-1. PMID: 42050709; PMCID: PMC13126800. https://pmc.ncbi.nlm.nih.gov/articles/PMC13126800/ (Full text)

An Overview of Severe Myalgic Encephalomyelitis

Abstract:

In this article, we have reviewed the literature on severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a clinical diagnosis in the absence of a diagnostic test. However, in research settings and disability disputes, 2-day cardiopulmonary exercise testing can be used to diagnose and document the abnormal response to exercise. Biomedical research into this disease has been scarce and underfunded for decades. Consequently, there are no effective treatments.

In its most severe form, it is more disabling than many other diseases, and patients are bedbound 24/7, dependent on carers, and spend their days in dark and quiet rooms. Even the soft sound of a human voice can lead to further deterioration. Some of the very severely ill suffer from life-threatening malnutrition and need to be tube-fed. The COVID-19 pandemic has led to a sharp increase in the number of patients with post-infectious diseases, and many of them fulfill ME/CFS criteria.

Dedicated, focused research using advanced medical technologies is needed to gain further understanding of the underlying disease mechanism. This will enable us to find effective pharmacological treatments and address the unmet medical needs of these very ill people.

Source: Vink M, Vink-Niese A. An Overview of Severe Myalgic Encephalomyelitis. J Clin Med. 2026 Jan 19;15(2):805. doi: 10.3390/jcm15020805. PMID: 41598742. https://www.mdpi.com/2077-0383/15/2/805 (Full text)

The influence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) family history on patients with ME/CFS

Abstract:

Aim: It is unclear if individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with family histories of ME/CFS differ from those with ME/CFS without this family history. To explore this issue, quantitative data from patients with ME/CFS and controls were collected, and we examined those with and without family histories of ME/CFS.

Methods: The samples included 400 patients with ME/CFS, and a non-ME/CFS chronic illness control group of 241 patients with multiple sclerosis (MS) and 173 with post-polio syndrome (PPS).

Results: Confirming findings from prior studies, those with ME/CFS were more likely to have family members with ME/CFS than controls. We found family histories of ME/CFS were significantly higher (18%) among the ME/CFS group than the non-ME/CFS controls (3.9%). In addition, patients with ME/CFS who had family histories of ME/CFS were more likely to have gastrointestinal symptoms than those with ME/CFS without those family histories.

Conclusions: Given the recent reports of gastrointestinal difficulties among those with ME/CFS, our findings might represent one predisposing factor for the emergence of ME/CFS.

Source: Jason LA, Ngonmedje S. The influence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) family history on patients with ME/CFS. Explor Med. 2024;5(2):185-192. doi: 10.37349/emed.2024.00215. Epub 2024 Apr 11. PMID: 39502189; PMCID: PMC11537498. https://pmc.ncbi.nlm.nih.gov/articles/PMC11537498/ (Full text)

The influence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) family history on patients with ME/CFS

Abstract:

Aim: It is unclear if individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with family histories of ME/CFS differ from those with ME/CFS without this family history. To explore this issue, quantitative data from patients with ME/CFS and controls were collected, and we examined those with and without family histories of ME/CFS.

Methods: The samples included 400 patients with ME/CFS, and a non-ME/CFS chronic illness control group of 241 patients with multiple sclerosis (MS) and 173 with post-polio syndrome (PPS).

Results: Confirming findings from prior studies, those with ME/CFS were more likely to have family members with ME/CFS than controls. We found family histories of ME/CFS were significantly higher (18%) among the ME/CFS group than the non-ME/CFS controls (3.9%). In addition, patients with ME/CFS who had family histories of ME/CFS were more likely to have gastrointestinal symptoms than those with ME/CFS without those family histories.

Conclusions: Given the recent reports of gastrointestinal difficulties among those with ME/CFS, our findings might represent one predisposing factor for the emergence of ME/CFS.
Source: Jason LA, Ngonmedje S. The influence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) family history on patients with ME/CFS. Explor Med. 2024;5:185–92. https://doi.org/10.37349/emed.2024.00215 https://www.explorationpub.com/Journals/em/Article/1001215 (Full text)

The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives

Abstract:

Like other infections, a SARS-CoV-2 infection can also trigger Post-Acute Infection Syndromes (PAIS), which often progress into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS, characterized by post-exercise malaise (PEM), is a severe multisystemic disease for which specific diagnostic markers or therapeutic concepts have not been established.

Despite numerous indications of post-infectious neurological, immunological, endocrinal, and metabolic deviations, the exact causes and pathophysiology remain unclear. To date, there is a paucity of data, that changes in the composition and function of the gastrointestinal microbiota have emerged as a potential influencing variable associated with immunological and inflammatory pathways, shifts in ME/CFS. It is postulated that this dysbiosis may lead to intestinal barrier dysfunction, translocation of microbial components with increased oxidative stress, and the development or progression of ME/CFS.

In this review, we detailed discuss the findings regarding alterations in the gastrointestinal microbiota and its microbial mediators in ME/CFS. When viewed critically, there is currently no evidence indicating causality between changes in the microbiota and the development of ME/CFS. Most studies describe associations within poorly defined patient populations, often combining various clinical presentations, such as irritable bowel syndrome and fatigue associated with ME/CFS.

Nevertheless, drawing on analogies with other gastrointestinal diseases, there is potential to develop strategies aimed at modulating the gut microbiota and/or its metabolites as potential treatments for ME/CFS and other PAIS. These strategies should be further investigated in clinical trials.

Source: Andreas Stallmach, Stefanie Quickert, Christian Puta, Philipp A. Reuken. The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives. Front. Immunol., 27 March 2024, Sec. Microbial Immunology, Volume 15 – 2024. https://doi.org/10.3389/fimmu.2024.1352744 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1352744/full (Full text)

Clinical features of Japanese patients with gastrointestinal long-COVID symptoms

Introduction:

Although the development of new therapeutic approaches and vaccines has decreased coronavirus disease 2019 (COVID-19)-associated mortality, prolonged systemic symptoms after COVID-19, termed long-COVID, have been a major concern, considering their potential impact on health-related quality of life (QOL). Gastrointestinal (GI) symptoms, including diarrhea and abdominal pain, have been reported in patients with long-COVID even months after the initial COVID-19 symptoms have resolved.

Although emerging evidence suggests that GI symptoms in long-COVID are affected by the dysregulation of the immune system or ongoing inflammation and damage to the GI tract caused by the initial COVID-19 infection, the clinical features of patients with GI long-COVID symptoms remain elusive. Our study aimed to clarify these features.

Source: Kazuma Yagi, Takanori Asakura, Hideki Terai, Keiko Ohgino, Katsunori Masaki, Ho Namkoong, Shotaro Chubachi, Jun Miyata, Ichiro Kawada, Nobuhiro Kodama, Satoshi Sakamoto, Akira Umeda, Takashi Ishiguro, Makoto Ishii, Koichi Fukunaga. JGH Open. First published: 06 December 2023 https://doi.org/10.1002/jgh3.13006 https://onlinelibrary.wiley.com/doi/full/10.1002/jgh3.13006 (Full text)

Post-COVID-19 and Irritable Bowel Syndrome: A Literature Review

Abstract:

The emergence of post-COVID-19 syndrome (PCS), a complex and multifactorial condition that follows the acute COVID-19 infection, has raised serious concerns within the global medical community. Concurrently, Irritable Bowel Syndrome (IBS), a widespread chronic gastrointestinal (GI) dysfunction, is considered to be one of the most common disorders of gut–brain interaction (DGBI) that significantly affects the quality of life and social functioning of patients. PCS presents a wide range of symptoms and GI manifestations, including IBS.
This review aims to analyze the GI involvement and the prolonged symptoms of COVID-19 infection as part of PCS, in order to explore the potential development of post-infection IBS (PI-IBS) in COVID-19 patients. Irritating factors such as enteric infection, psychosocial conditions, food antigens, and antibiotics may lead to abnormalities in the physiological function of the GI system and could be involved in the development of PI-IBS. Through the presentation of the pathophysiological mechanisms and epidemiological studies that assessed the prevalence of IBS as part of PCS, we attempted to provide a better understanding of the long-term consequences of COVID-19 and the pathogenesis of PI-IBS.
Even though PI-IBS is becoming a global challenge, there are only a few studies about it and therefore limited knowledge. Currently, the majority of the existing treatment options are referred to non-COVID-19-associated DGBIs. Forthcoming studies may shed light on the mechanisms of PI-IBS that could be targeted for treatment development. Paramythiotis D, Karlafti E, Didagelos M, Fafouti M, Veroplidou K, Protopapas AA, Kaiafa G, Netta S, Michalopoulos A, Savopoulos C. Post-COVID-19 and Irritable Bowel Syndrome: A Literature Review. Medicina. 2023; 59(11):1961. https://doi.org/10.3390/medicina59111961 https://www.mdpi.com/1648-9144/59/11/1961 (Full text)
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Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study

Abstract:

Objective: To determine if patients that develop lingering neurologic symptoms of fatigue and “brain fog” after initial recovery from coronavirus disease 2019 (COVID-19) have persistent low growth hormone (GH) secretion as seen in other conditions with similar symptom etiology.

Design: In this case-control observational pilot study, patients reporting lingering neurologic post-acute sequelae of SARS-CoV-2 (PASC, n = 10) symptoms at least 6 months after initial infection were compared to patients that recovered from COVID-19 without lingering symptoms (non-PASC, n = 13). We compared basic blood chemistry and select metabolites, lipids, hormones, inflammatory markers, and vitamins between groups. PASC and non-PASC subjects were tested for neurocognition and GH secretion, and given questionnaires to assess symptom severity. PASC subjects were also tested for glucose tolerance and adrenal function.

Results: PASC subjects reported significantly worse fatigue, sleep quality, depression, quality of life, and gastrointestinal discomfort compared to non-PASC. Although PASC subjects self-reported poor mental resilience, cognitive testing did not reveal significant differences between groups. Neurologic PASC symptoms were not linked to inflammatory markers or adrenal insufficiency, but were associated with reduced growth hormone secretion.

Conclusions: Neurologic PASC symptoms are associated with gastrointestinal discomfort and persistent disruption of GH secretion following recovery from acute COVID-19.

Source: Wright TJ, Pyles RB, Sheffield-Moore M, Deer RR, Randolph KM, McGovern KA, Danesi CP, Gilkison CR, Ward WW, Vargas JA, Armstrong PA, Lindsay SE, Zaidan MF, Seashore J, Wexler TL, Masel BE, Urban RJ. Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study. Mol Cell Endocrinol. 2023 Oct 8:112071. doi: 10.1016/j.mce.2023.112071. Epub ahead of print. PMID: 37816478. https://www.sciencedirect.com/science/article/abs/pii/S0303720723002228

Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts

Abstract:

Background: The respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a multi-organ disorder, with long-term effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease (COVID).

Aim: To examine the current knowledge and outcomes of long-term neurological and gastrointestinal (GI) symptoms in adult cohorts, including United States minority populations.

Methods: PubMed and Google Scholar were searched using relevant terms, and data from five studies were analyzed, comprising 27383 patients with persistent neurological and GI sequelae.

Results: The main symptoms included anxiety, depression, dysphagia, headache, vomiting, nausea, gastroesophageal reflux, fatigue, and abdominal pain. Patients with comorbidities and metabolic syndromes were at higher risk for long COVID. While most patients were European Americans, there was a need for further study on African Americans.

Conclusion: The underlying causes of these symptoms remain unclear, warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.

Source: Sherif ZA, Deverapalli M, Challa SR, Martirosyan Z, Whitesell P, Pizuorno AM, Naqvi Z, Tulloch IK, Oskrochi G, Brim H, Ashktorab H. Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts. World J Methodol. 2023 Sep 20;13(4):323-336. doi: 10.5662/wjm.v13.i4.323. PMID: 37771866; PMCID: PMC10523249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523249/ (Full text)