Tag: dysbiosis

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

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disorder characterized by immune dysregulation, metabolic impairments, neuroendocrine disturbances, endothelial dysfunction, and gastrointestinal abnormalities.

Immune alterations include reduced natural killer cell cytotoxicity, T-cell exhaustion, abnormal B-cell subsets, and the presence of diverse autoantibodies, suggesting an autoimmune component.

Gut dysbiosis and increased intestinal permeability may promote systemic inflammation and contribute to neurocognitive symptoms via the gut-brain axis. Neuroendocrine findings such as hypothalamic-pituitary-adrenal (HPA) axis hypofunction and altered thyroid hormone metabolism further compound metabolic and immune abnormalities.

Metabolomic and mitochondrial studies identify impaired ATP generation, redox imbalance, and compensatory shifts toward alternative energy pathways underlying hallmark symptoms like post-exertional malaise.

Endothelial dysfunction driven by oxidative and nitrosative stress, along with autoantibody-mediated receptor interference, may explain orthostatic intolerance and impaired perfusion. Collectively, ME/CFS appears to arise from a self-sustaining cycle of chronic inflammation, metabolic insufficiency, and neuroimmune imbalance.

Source: Dudova D, Bozhkova M, Petrov S, Nikolova R, Kalfova T, Ivanovska M, Vaseva K, Nikolova M, Ivanov IN. Insights into the Complex Biological Network Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int J Mol Sci. 2025 Dec 26;27(1):268. doi: 10.3390/ijms27010268. PMID: 41516145; PMCID: PMC12785471. https://pmc.ncbi.nlm.nih.gov/articles/PMC12785471/ (Full text)

Multi-Strain Probiotic Improves Tryptophan Metabolism and Symptoms in Chronic Fatigue Syndrome Patients with Co-Occurring Irritable Bowel Syndrome: An Open-Label Pilot Study

Simple Summary:

Chronic Fatigue Syndrome (CFS) is a debilitating condition often accompanied by gut health issues, but effective treatments are scarce. Recent research suggests that an imbalance in gut bacteria (dysbiosis) may contribute to CFS symptoms by producing harmful substances that affect the nervous system. We investigated whether a specific multi-strain probiotic (CDS22-formula) could improve symptoms in women with CFS and co-occurring IBS. Over 12 weeks, patients took a high-dose probiotic supplement. We monitored their fatigue levels and analyzed urine samples to track changes in tryptophan metabolism—a key pathway linking the gut to the brain. The results showed that the probiotic intervention was associated with an improved gut bacteria profile. Importantly, this coincided with a reduction in neurotoxic metabolites and a significant decrease in fatigue severity. Our findings suggest that targeting the gut microbiome can be a valuable strategy for managing chronic fatigue, potentially by modulating the production of metabolites that affect brain function.
Abstract:

Background/Objectives: Gut dysbiosis in Chronic Fatigue Syndrome (CFS) drives low-grade inflammation and shifts tryptophan metabolism toward neurotoxic pathways. The causal link between bacterial translocation, kynurenine pathway dysregulation, and symptom severity remains under-defined. We evaluated the impact of a high-concentration multi-strain probiotic on the “gut-kynurenine axis” and clinical status in CFS patients with co-morbid IBS-U and confirmed dysbiosis.
Methods: Forty female patients with confirmed dysbiosis (GA-map™ Dysbiosis Index > 2) received the CDS22 formula (450 billion CFU/day) for 12 weeks. We compared urinary tryptophan metabolite profiles (LC-MS/MS), gut dysbiosis markers (3-indoxyl sulfate), and fatigue severity (FSS) against 40 age-matched healthy controls.
Results: Baseline analysis revealed profound metabolic perturbations: elevated bacterial proteolytic markers (3-IS), substrate depletion (low tryptophan), and a neurotoxic signature (high quinolinic acid [QA], low kynurenic acid [KYNA]). Following the intervention, fatigue scores declined by 40.3%, with 97.5% of patients reaching the remission threshold (FSS < 36). Biochemically, 3-IS levels decreased to the range observed in healthy controls and attenuated xanthurenic acid levels. Although absolute QA concentrations remained elevated compared to controls, the neuroprotective KYNA/QA ratio increased significantly (+45%). Increased systemic tryptophan availability correlated directly with clinical symptom reduction (Spearman’s rho = −0.36, p = 0.024).
Conclusions: The CDS22 formulation was associated with a restoration of intestinal eubiosis and functional tryptophan partitioning. Clinical remission coincides with a metabolic shift favoring neuroprotection (increased KYNA/QA ratio), validating the gut–kynurenine axis as a modifiable therapeutic target. Peripheral metabolic improvement relative to the healthy baseline appeared sufficient for symptom relief in this specific phenotype, despite incomplete clearance of neurotoxic metabolites.
Source:

The gut microbial composition is different in chronic fatigue syndrome than in healthy controls

Abstract:

The pathogenesis of Chronic Fatigue Syndrome (CFS) is yet unknown. This study aimed to assess the gut microbial composition in CFS patients versus in healthy controls (HCs).

The composition of fecal bacteria was examined in twenty-five CFS patients and sixteen HCs using Illumina sequencing of 16 S rRNA gene amplicons targeting the V3-V4 bacterial gene regions. 143 (46%) of the microbial genera were found only in the CFS. In addition, the gut microbial composition in the CFS patients contained a much higher proportion of the 10 most commonly found bacteria compared to the HCs group. A significantly lower observed number of operational taxonomic units (OTUs) was noted in CFS compared to HCs (p = 0.045).

Significant between-group differences in the gut microbial composition in CFS compared to HCs were noted. The three most discriminating Amplicon Sequencing Variants (ASVs): ASV 191, ASV 44, and ASV 75, were identified as significantly more abundant in the healthy control group compared to the patient group. In addition, the Neural Network (multilayer perceptron) was able to discriminate gut microbial composition from CFS versus HCs with excellent performance (AUC = 0.935).

The gut microbial composition is different in CFS patients compared to HCs. Further studies should assess the pathophysiological consequences of these differences as well as the effectiveness of therapies aimed at modifying the gut microbial composition in CFS patients.

Source: Prylińska-Jaśkowiak M, Tabisz H, Kujawski S, Godlewska BR, Słomko J, Januszko-Giergielewicz B, Murovska M, Morten KJ, Sokołowski Ł, Zalewski P. The gut microbial composition is different in chronic fatigue syndrome than in healthy controls. Sci Rep. 2025 Sep 26;15(1):33075. doi: 10.1038/s41598-025-16438-y. PMID: 41006438. https://www.nature.com/articles/s41598-025-16438-y (Full text)

Plasma taurine level is linked to symptom burden and clinical outcomes in post-COVID condition

Abstract:

Background: A subset of individuals (10-20%) experience post-COVID condition (PCC) subsequent to initial SARS-CoV-2 infection, which lacks effective treatment. PCC carries a substantial global burden associated with negative economic and health impacts. This study aims to evaluate the association between plasma taurine levels with self-reported symptoms and adverse clinical outcomes in patients with PCC.

Methods and findings: We analyzed the plasma proteome and metabolome of 117 individuals during their acute COVID-19 hospitalization and at the convalescence phase six-month post infection. Findings were compared with 28 age and sex-matched healthy controls. Plasma taurine levels were negatively associated with PCC symptoms and correlated with markers of inflammation, tryptophan metabolism, and gut dysbiosis. Stratifying patients based on the trajectories of plasma taurine levels during six-month follow-up revealed a significant association with adverse clinical events. Increase in taurine levels during the transition to convalescence were associated with a reduction in adverse events independent of comorbidities and acute COVID-19 severity. In a multivariate analysis, increased plasma taurine level between acute and convalescence phase was associated with marked protection from adverse clinical events with a hazard ratio of 0.13 (95% CI: 0.05-0.35; p<0.001).

Conclusions: Taurine emerges as a promising predictive biomarker and potential therapeutic target in PCC. Taurine supplementation has already demonstrated clinical benefits in various diseases and warrants exploration in large-scale clinical trials for alleviating PCC.

Source: Khoramjoo M, Wang K, Srinivasan K, Gheblawi M, Mandal R, Rousseau S, Wishart D, Prasad V, Richer L, Cheung AM, Oudit GY. Plasma taurine level is linked to symptom burden and clinical outcomes in post-COVID condition. PLoS One. 2024 Jun 5;19(6):e0304522. doi: 10.1371/journal.pone.0304522. PMID: 38837993; PMCID: PMC11152273. https://pmc.ncbi.nlm.nih.gov/articles/PMC11152273/ (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disease characterised by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains one of the most understudied and misunderstood conditions in modern medicine. ME/CFS lacks standardised diagnostic criteria owing to variations in both inclusion and exclusion criteria across different diagnostic guidelines, and furthermore, there are currently no effective treatments available.

Moving beyond the traditional fragmented perspectives that have limited our understanding and management of the disease, our analysis of current information on ME/CFS represents a significant paradigm shift by synthesising the disease’s multifactorial origins into a cohesive model. We discuss how ME/CFS emerges from an intricate web of genetic vulnerabilities and environmental triggers, notably viral infections, leading to a complex series of pathological responses including immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances.

This comprehensive model not only advances our understanding of ME/CFS’s pathophysiology but also opens new avenues for research and potential therapeutic strategies. By integrating these disparate elements, our work emphasises the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease’s complexity and the multifaceted approach required for its study and management.

Source: Arron HE, Marsh BD, Kell DB, Khan MA, Jaeger BR, Pretorius E. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease. Front Immunol. 2024 Jun 3;15:1386607. doi: 10.3389/fimmu.2024.1386607. PMID: 38887284; PMCID: PMC11180809. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180809/ (Full text)

An approach to finding specific forms of dysbiosis that associate with different disorders

Abstract:

Background Many disorders display dysbiosis of the enteric microbiome, compared with healthy controls. Different disorders share a pattern of dysbiosis that may reflect ‘reverse causation’, due to non-specific effects of illness-in-general. Combining a range of disorders into an ‘aggregate non-healthy active control’ (ANHAC) group should highlight such non-specific dysbiosis. Differential dysbiosis between the ANHAC group and specific disorders may then reflect effects of treatment or bowel dysfunction, or may potentially be causal. Here, we illustrate this logic by testing if individual genera can differentiate an ANHAC group from two specific diagnostic groups.

Methods We constructed an ANAHC group (n=17) that had 14 different disorders. We then used random forest analyses to test differential dysbiosis between the ANHAC group and two other disorders that have no known pathology, but: (i) symptoms of illness (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome – ME/CFS – n = 38); or (ii) both illness and bowel dysfunction (ME/CFS comorbid with Irritable Bowel Syndrome – IBS – n=27).

Results Many genera differentiated the ANHAC group from co-morbid IBS. However, only two genera – Roseburia and Dialister – discriminated the ANHAC group from ME/CFS.

Conclusions Different disorders can associate with specific forms of dysbiosis, over-and-above non-specific effects of illness-in-general. Bowel dysfunction may contribute to dysbiosis in IBS via reverse causation. However, ME/CFS has symptoms of illness-in-general, but lacks known pathology or definitive treatment that could cause dysbiosis. Therefore, the specific dysbiosis in ME/CFS may be causal. [230 words]

Contribution to the field Many disorders associate with enteric dysbiosis. The pattern of dysbiosis is largely consistent between unrelated disorders, which suggests that it mainly reflects non-specific secondary effects of illness-in-general (e.g. due to changes in activity levels, or diet). However, faecal microbiome transplantation (FMT) can be therapeutic in some disorders. This implies that unique features of dysbiosis may cause those specific disorders. Here, we propose a way to assess causal effects of dysbiosis, by testing if individual genera can discriminate individual disorders from an ‘aggregate non-healthy active control’ (ANHAC) group. Dysbiosis in the ANHAC group can control for non-specific effects of illness-in-general on the microbiome and so highlight potentially-causal forms of dysbiosis in specific disorders. This approach may provide insight into pathogenetic mechanisms of individual disorders and help to design specific forms of FMT to counteract them.

Source: Jonathan Williams, Inga Williams, Karl Morten, Julian Kenyon. An approach to finding specific forms of dysbiosis that associate with different disorders. medRxiv 2024.04.23.24306162; doi: https://doi.org/10.1101/2024.04.23.24306162 https://www.medrxiv.org/content/10.1101/2024.04.23.24306162v1 (Full text available as PDF file)

Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness often triggered by an initiating acute event, mainly viral infections. The transition from acute to chronic disease remains unknown, but interest in this phenomenon has escalated since the COVID-19 pandemic and the post-COVID-19 illness, termed ‘long COVID’ (LC). Both ME/CFS and LC share many clinical similarities.

Here, we present recent findings in ME/CFS research focussing on proposed disease pathologies shared with LC. Understanding these disease pathologies and how they influence each other is key to developing effective therapeutics and diagnostic tests. Given that ME/CFS typically has a longer disease duration compared with LC, with symptoms and pathologies evolving over time, ME/CFS may provide insights into the future progression of LC.

Source: Annesley SJ, Missailidis D, Heng B, Josev EK, Armstrong CW. Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies. Trends Mol Med. 2024 Mar 4:S1471-4914(24)00028-5. doi: 10.1016/j.molmed.2024.02.003. Epub ahead of print. PMID: 38443223. https://www.sciencedirect.com/science/article/pii/S1471491424000285 (Full text)

Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach

Abstract:

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin.

This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

Source: Chambers, P.W.; Chambers, S.E. Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach. Preprints 2023, 2023121881. https://doi.org/10.20944/preprints202312.1881.v2 https://www.preprints.org/manuscript/202312.1881/v2 (Full text available as PDF file)

Inflammation-type dysbiosis of the oral microbiome associates with the duration of COVID-19 symptoms and long COVID

Abstract:

In the COVID-19 pandemic, caused by SARS-CoV-2, many individuals experience prolonged symptoms, termed long-lasting COVID-19 symptoms (long COVID). Long COVID is thought to be linked to immune dysregulation due to harmful inflammation, with the exact causes being unknown. Given the role of the microbiome in mediating inflammation, we aimed to examine the relationship between the oral microbiome and the duration of long COVID symptoms.

Tongue swabs were collected from patients presenting with COVID-19 symptoms. Confirmed infections were followed until resolution of all symptoms. Bacterial composition was determined by metagenomic sequencing. We used random forest modeling to identify microbiota and clinical covariates that are associated with long COVID symptoms. Of the patients followed, 63% developed ongoing symptomatic COVID-19 and 37% went on to long COVID.

Patients with prolonged symptoms had significantly higher abundances of microbiota that induced inflammation, such as members of the genera Prevotella and Veillonella, which, of note, are species that produce LPS. The oral microbiome of patients with long COVID was similar to that of patients with chronic fatigue syndrome.

Altogether, our findings suggest an association with the oral microbiome and long COVID, revealing the possibility that dysfunction of the oral microbiome may have contributed to this draining disease.

Source: Haran JP, Bradley E, Zeamer AL, Cincotta L, Salive MC, Dutta P, Mutaawe S, Anya O, Meza-Segura M, Moormann AM, Ward DV, McCormick BA, Bucci V. Inflammation-type dysbiosis of the oral microbiome associates with the duration of COVID-19 symptoms and long COVID. JCI Insight. 2021 Oct 22;6(20):e152346. doi: 10.1172/jci.insight.152346. PMID: 34403368; PMCID: PMC8564890. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564890/ (Full text)

Links between Serotonin Levels and Stress: Cortisol, Candida A./Mycetes, Omega 3/6 Ratio and Dysbiosis (Skatole/Indoxyl Sulfate) Role in Chronic Fatigue Syndrome (CFS) and Depression

Abstract:

Intestinal microbiota attracts daily attention of a growing number of study which have attempted to link gut dysbiosIs with a variety of disease states: irritable bowel syndrome (IBS), inflamed bowel disease (IBD), Crohn’s disease (CD), leaky gut syndrome (LGS), food intolerance, diabetes, metabolic syndrome, cancer, etc.

In our study we analyzed how intestinal dysbiosis may be related to chronic fatigue syndrome (CFS) and depression through the exchange of information through the gut-brain axis (GBA).

We studied 33 subjects, 13 males and 20 females, who reported CFS or/and depression: we investigated their salivary cortisol levels, blood serotonin, omega 3/6 ratio, intestinal dysbiosis (calculated on the urinary levels of indoxyl sulfate and skatole), and we looked for the presence of Candida a. or mycetes in the stool; the data accumulated with this research show a correlation between the presence of Candida a./miceti, indoxyl sulfate urine values beyond the physiological and low serotonin levels.

In addition, data analysis showed that the EPA/DHA values also show pro-inflammatory levels in case of dysbiosis and low serotonina levels. The relationship, however, with cortisol levels requires further research although this study showed a statistically significant positive correlation between these values, measured at specific times, and serotonin levels.

Aims: We investigated the relationship between stress (evaluated through the measurement of salivary cortisol levels) and gastrointestinal efficiency measured as a function of intestinal fermentative and putrefactive dysbiosis, evaluating the levels of urinary indoxyl sulfate in the first case (a possible correlation with the presence of Candida spp or Mycetes in the subjects feces was investigated), urinary skatole levels in the second one, in patients with chronic fatigue syndrome (SFC) and depression.

In these patients we also have studied omega 3/6 ratio, and finally we have analized the impact that the alteration of these parameters can have on the serotonin levels.

This research attemps to highlight the contact points, in some cases not so obvious, among these topics, contact points that, although they give us interesting indications, show the need to be further deepened by analyzing a larger amount of data.

Source: Orlandoni, D.; Di Fede, G.; Mantovani, M.; Nava, C.R.; Tomasi, M.; Fusi, P. Links between Serotonin Levels and Stress: Cortisol, Candida A./Mycetes, Omega 3/6 Ratio and Dysbiosis (Skatole/Indoxyl Sulfate) Role in Chronic Fatigue Syndrome (CFS) and Depression. Preprints 2023, 2023090253. https://doi.org/10.20944/preprints202309.0253.v1 https://www.preprints.org/manuscript/202309.0253/v1 (Full text available as PDF file)