Eukaryotes in the gut microbiota in myalgic encephalomyelitis/chronic fatigue syndrome

Mandarano, Alexandra H; Giloteaux, Ludovic; Keller, Brad M.; Levine, Susan; Hanson, Maureen R.

doi:10.7717/peerj.4282

Cited by 36 publications

(43 citation statements)

References 38 publications

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“…Interestingly enough, Roux et al 97 presented a catalog of DE lncRNAs after exposure of human monocytes, macrophages, epithelium, and chondrocytes to proinflammatory lipopolysaccharides (LPS) or interleukin-1b, finding 204 human DE lncRNAs with activation of immune response. Exposure to LPS ("leaky gut") has been proposed by some authors as a potential factor contributing to ME/CFS, 98,99 and evaluation of a potential association of these 204 inflammation-linked lncRNAs to ME/CFS might therefore be relevant. Moreover, when Roux et al searched for lncRNAs, mouse synteny of lncRNAs associated with LPS challenge obtained only 21 hits, which may lie at the core of the response.…”

Section: April 2019mentioning

confidence: 99%

Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation

Almenar-Pérez

Ovejero

Sánchez-Fito

et al. 2019

Clinical Therapeutics

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Purpose: Studies to determine epigenetic changes associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain scarce; however, current evidence clearly shows that methylation patterns of genomic DNA and noncoding RNA profiles of immune cells differ between patients and healthy subjects, suggesting an active role of these epigenetic mechanisms in the disease. The present study compares and contrasts the available ME/CFS epigenetic data in an effort to evidence overlapping pathways capable of explaining at least some of the dysfunctional immune parameters linked to this disease. Methods: A systematic search of the literature evaluating the ME/CFS epigenome landscape was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Differential DNA methylation and noncoding RNA differential expression patterns associated with ME/CFS were used to screen for the presence of transposable elements using the Dfam browser, a search program nurtured with the Repbase repetitive sequence database and the RepeatMasker annotation tool. Findings: Unexpectedly, particular associations of transposable elements and ME/CFS epigenetic hallmarks were uncovered. A model for the disease emerged involving transcriptional induction of endogenous dormant transposons and structured cellular RNA interactions, triggering the activation of the innate immune system without a concomitant active infection. Implications: Repetitive sequence filters (ie, RepeatMasker) should be avoided when analyzing transcriptomic data to assess the potential participation of repetitive sequences ("junk repetitive DNA"), representing >45% of the human genome, in the onset and evolution of ME/CFS. In addition, transposable element screenings aimed at designing cost-effective, focused empirical assays that can confirm or disprove the suspected involvement of transposon transcriptional activation in this disease, following the pilot strategy presented here, will require databases gathering large ME/CFS epigenetic datasets.

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Section: April 2019mentioning

confidence: 99%

Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation

Almenar-Pérez

Ovejero

Sánchez-Fito

et al. 2019

Clinical Therapeutics

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“…Gut microbiota and physiology • Widely reported disturbances to the gut microbiota [12,103,[115][116][117]119,120,184] and gut hyperpermeability [103,123,124].…”

Section: B Cellsmentioning

confidence: 99%

Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Missailidis¹,

Annesley²,

Fisher³

2019

Preprint

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The underlying molecular basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is not well understood. Characterized by chronic, unexplained fatigue, a disabling payback following exertion ("post-exertional malaise") and variably presenting, multi-system symptoms, ME/CFS is a complex disease which demands a concerted biomedical investigation from disparate fields of expertise. ME/CFS research and patient treatment have been challenged by the lack of diagnostic biomarkers and finding these is a prominent direction of current work. Despite these challenges, modern research demonstrates a tangible biomedical basis for the disorder across many body systems. This evidence is mostly comprised of disturbances to immunological and inflammatory pathways, autonomic and neurological dysfunction, abnormalities in muscle and mitochondrial function, shifts in metabolism, and gut physiology or gut microbiota disturbances. It is possible that these threads are together entangled as parts of an underlying molecular pathology reflecting a farreaching homeostatic shift. Due to the variability of non-overlapping symptom presentation or precipitating events such as infection or other bodily stresses, the initiation of body-wide pathological cascades with similar outcomes stemming from different causes may be implicated in the condition. Patient stratification to account for this heterogeneity is therefore one important consideration during exploration of potential diagnostic developments.compounded by medical guidelines in some developed countries which are out of date regarding ME/CFS clinical practice and require urgent, overdue revision.Case definitions such as the commonly termed Oxford [1] or Fukuda [2] criteria are most often utilized throughout the UK and USA respectively, yet may fail to discriminate between generalized chronic fatigue and ME/CFS which specifically also involves PEM, which aids in characterizing this disorder as a discrete clinical entity. Also in usage are the Canadian Consensus Criteria [3] and International Consensus Criteria [4] which mandate PEM for a diagnosis of ME/CFS and therefore may be considered more specific definitions. While the presence of PEM is an optional component of the Fukuda criteria, PEM is, unfortunately, not required for research participation by all studies using this or other less strict definitions. Consequently, the discovery of a reliable diagnostic biomarker is perhaps the most common recurring theme in modern ME/CFS research. Despite myriad relevant study outcomes [5][6][7][8][9][10][11][12][13][14][15][16], no such discovery has yet been widely validated or implemented as a suitable diagnostic biomarker of ME/CFS. Not only does ME/CFS affect multiple body systems and organs, but it does so with different and time-varying levels of severity and different patterns of comorbidities in different individuals, thereby producing a highly heterogeneous patient population [7,[17][18][19][20][21][22][23]. This complexity represents a major challenge to the task of incrim...

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“…Investigations of the metabolome (16)(17)(18)(19)(20) and (gut) microbiome (21)(22)(23)(24)(25) in CFS, both aspects that are inadvertently linked with in ammation (16,26), showed interesting, albeit inconsistent, results (23,25). Up until this moment, no such studies were conducted in QFS.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics Examination of Q Fever Fatigue Syndrome Identifies Similarities with Chronic Fatigue Syndrome

Raijmakers

Roerink

Jansen

et al. 2020

Preprint

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Background: Q fever fatigue syndrome (QFS) is characterised by a state of prolonged fatigue that is seen in 20% of acute Q fever infections and has major health-related consequences. The molecular mechanisms underlying QFS are largely unclear. In order to better understand its pathogenesis, we applied a multi-omics approach to study the patterns of the gut microbiome, blood metabolome, and inflammatory proteome of QFS patients, and compared these with those of chronic fatigue syndrome (CFS) patients and healthy controls (HC). Methods: The study population consisted of 31 QFS patients, 50 CFS patients, and 72 HC. All subjects were matched for age, gender, and general geographical region (South-East part of the Netherlands). The gut microbiome composition was assessed by Metagenomic sequencing using the Illumina HiSeq platform. A total of 92 circulating inflammatory markers were measured using Proximity Extension Essay and 1607 metabolic features were assessed with a high-throughput non-targeted metabolomics approach. Results: Inflammatory markers, including 4E-BP1 (P = 9.60-16 and 1.41-7) and MMP-1 (P = 7.09-9 and 3.51-9), are significantly more expressed in both QFS and CFS patients compared to HC, and QFS patients show more of an inflammatory profile than CFS patients and HC. Blood metabolite profiles show significant differences when comparing QFS (319 metabolites) and CFS (441 metabolites) patients to HC, and are significantly enriched in pathways like sphingolipid (P = 0.0256 and 0.0033) metabolism. When comparing QFS to CFS patients, almost no significant differences in metabolome were found. Comparison of microbiome taxonomy of QFS and CFS patients with that of HC, shows both in- and decreases in abundancies in Bacteroidetes (with emphasis on Bacteroides and Alistiples spp.), and Firmicutes and Actinobateria (with emphasis on Ruminococcus and Bifidobacterium spp.). When we compare QFS patients to CFS patients, there is a striking resemblance and hardly any significant differences in microbiome taxonomy are found. Conclusions: We show that QFS and CFS patients are similar across three different omics layers and 4E-BP1 and MMP-1 have the potential to distinguish QFS and CFS patients from HC.

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Eukaryotes in the gut microbiota in myalgic encephalomyelitis/chronic fatigue syndrome

Cited by 36 publications

References 38 publications

Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation

Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation

Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Multi-omics Examination of Q Fever Fatigue Syndrome Identifies Similarities with Chronic Fatigue Syndrome

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