The association of fecal microbiota & fecal, blood serum & urine metabolites in ME/CFS

Posted on 01/13/2017 by wames

Research abstract:

INTRODUCTION:

The human gut microbiota has the ability to modulate host metabolism. Metabolic profiling of the microbiota and the host biofluids may determine associations significant of a host–microbe relationship. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disorder of fatigue that is poorly understood, but has been linked to gut problems and altered microbiota.

OBJECTIVES

Find changes in fecal microbiota and metabolites in ME/CFS and determine their association with blood serum and urine metabolites.

METHODS

A workflow was developed that correlates microbial counts with fecal, blood serum and urine metabolites quantitated by high-throughput 1H NMR spectroscopy. The study consists of thirty-four females with ME/CFS (34.9 ± 1.8 SE years old) and twenty-five non-ME/CFS female (33.0 ± 1.6 SE years old).

RESULTS

The workflow was validated using the non-ME/CFS cohort where fecal short chain fatty acids (SCFA) were associated with serum and urine metabolites indicative of host metabolism changes enacted by SCFA.

In the ME/CFS cohort a decrease in fecal lactate and an increase in fecal butyrate, isovalerate and valerate were observed along with an increase in Clostridium spp. and a decrease in Bacteroides spp. These differences were consistent with an increase in microbial fermentation of fiber and amino acids to produce SCFA in the gut of ME/CFS patients. Decreased fecal amino acids positively correlated with substrates of gluconeogenesis and purine synthesis in the serum of ME/CFS patients.

CONCLUSION

Increased production of SCFA by microbial fermentation in the gut of ME/CFS patients may be associated with deleterious effects on the host energy metabolism.

The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome, by Christopher W. Armstrong, Neil R. McGregor, Donald, P. Lewis, Henry L. Butt, Paul R Gooley in Metabolomics, January 2017 13:8 [Published online 12 Dec 2016]

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The great NIH exercise initiative: a boon for ME/CFS & FM?

Posted on 01/12/2017 by wames

Health rising forum post, by Cort Johnson, 3 January 2017: The Great NIH Exercise Initiative: A Boon for Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia?

“This physical activity initiative aims to fundamentally change our understanding of what happens to the body on the molecular level when we exercise,” said James M. Anderson, M.D., Ph.D.

In Part II of a three-part look at recent major NIH efforts that may significantly impact chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) we find the NIH bringing its big guns to bear on the most problematic area of all for ME/CFS patients – exercise.

Few diseases, if any, are as defined by problems with physical activity as chronic fatigue syndrome (ME/CFS), and few diseases affect physical activity as dramatically as does fibromyalgia. Nobody, of course, knows why mild exercise can cause such relapse in ME/CFS or why more serious exercise can cause such pain in FM.

Maybe that’s not such a surprise. It turns out that researchers know surprisingly little about what happens when we exercise. Sure they know what happens to the heart rate, blood flows, air intake, oxygen usage, etc., when we exercise but we know very little about what happens to the body at the molecular level. That’s important, not just for exercise physiologists, but for ME/CFS and FM as well; it’s at the molecular level where the key to ME/CFS and FM probably lies.

Our understanding of the molecular changes that occur during exercise is going to entirely change – and probably fairly rapidly – when the NIH’s Molecular Transducers of Physical Activity in Humans Program (MoTrPAC; Motor…Pac – get it? Kind of?) gets rolling.

MotrPAC is going to take a deep dive into the world of exercise. By the time they’re done we’re going to have new ways to analyze what the heck goes wrong during exercise in ME/CFS.

You don’t think Dr. Collins wasn’t thinking of chronic fatigue syndrome (ME/CFS) when he said this:

“The development of a so-called molecular map of circulating signals produced by physical activity will allow us to discover, at a fundamental level, how physical activity affects our health. This knowledge should allow researchers and doctors to develop individually targeted exercise recommendations and better help those who are unable to exercise.”                                                  Francis Collins

I do… In fact, the optimist in me wonders if the fatigue RFA grant Collins was reportedly considering for ME/CFS morphed into this $170 million dollar (not completely funded) project. (Why would Collins do this kind of run-around? Because he can get buy-in from the Institutes to spend a ton of money to study exercise. He can’t get buy-in to spend that kind of money on ME/CFS.)

This is a biggie: it contains seven clinical sites, seven chemical analysis sites, animal models, a bioinformatics center, a coordination center, and finally and perhaps most importantly for diseases like chronic fatigue syndrome and fibromyalgia, the open sourced data information center.

Two of the 19 grants (Ron Davis and Dr. Montoya, take note) are going to two Stanford researchers (Michael Snyder, Stephen Montogomery) to identify and characterize all the molecules that form during or after exercise. Yes, that’s after exercise as well…what an opportunity to study post-exertional malaise in ME/CFS.

At the end of this huge grant ($15.7 million – equal to the entire budget of the upgraded NIH ME/CFS program) these two Stanford researchers will know more about genomic, transcriptomic and epigenomic effects of exercise than anyone else alive…and it’s all going to happen in the next five years.

One imagines that Nancy Klimas and Gordon Broderick with the multiple data points they’ve collected before, during and after exercise might have something to say to Drs. Michael Snyder and Stephen Montgomery, PhD. Of course, Dr. Montoya is using exercise in his immune studies at Stanford as well. One might think these researchers might be interested in the growing exercise data collected on the most exercise challenged illness group there is.

What an excellent control group ME/CFS patients would be (!). How better, after all, to explicate what goes right in exercise than by understanding what can go so wrong? Lead Stanford researcher Michael Snyder might very well agree:

“A lack of physical activity is a major factor in multiple diseases. This program provides an exciting opportunity to learn the molecular mechanisms underlying physical activity, with the goal of enabling new approaches to improving or maintaining individual health.”                                  Michael Snyder

Personally, I would put finding ways to enable ME/CFS patients to finally do the exercise they’ve been yearning for so many years as a top priority. One wonders how many ex-athletes – Jamison Hill’s and others – are out there? (Please take the survey.) Anecdotal reports suggest they abound in ME/CFS. Some people think ex-athletes may be over-expressed in ME/CFS. Thirty-seven years ago I was an avid runner and exerciser. Never did I dream such a fundamental part of my life could be taken away so completely.

Even if the Stanford group can’t find a way to include a few ME/CFS patients in their huge study, within five years or so we should have a bevy of molecular targets that Ron Davis, Derya Unutmaz, Patrick McGowan,Ian Lipkin, Gordon Broderick, Zaher Nahle or other ME/CFS researchers interested in the molecular roots of this disease should be able to analyze.
Stanford isn’t the only possible ME/CFS connection. Marcas Bamman at the University of Alabama at Birmingham’s “Center for Exercise Medicine” will lead one of the clinical centers. One wonders if he might be interested in what’s happening in Jarred Younger’s Neuroinflammation, Fatigue and Pain Lab on the same campus.

Plus, included in those omics’ (genomics, epigenomics, transcriptomics, proteomic’s) analyses are extensive metabolomics studies as well. MoTrPAC isn’t just whistling dixie with regard to metabolomics either. The Emory Chemical Analysis Center in Georgia appears to be almost entirely devoted to metabolomics. Boasting a “state-of-the-art ultra-high resolution accurate mass high-field Orbitrap tandem mass spectrometer”, the group will use “global, targeted and spatially resolved metabolomics” to produce “unequivocal chemical identification(s) of novel molecular transducers”. The Mayo Rochester site will also attempt to fuse proteomics and metabolomics date to generate molecular maps of physical activity.

What a serendipitous project this is. Just as ME/CFS research at the NIH starts to finally begin to ramp up (expect an announcement on that in the next couple of weeks) it embarks on an ambitious project to understand the molecular roots of the most problematic activity of all in ME/CFS – exercise. For once we have good timing.

Health Rising is a website with news blog and forums dedicated to providing timely, accurate information to people with chronic fatigue syndrome (ME/CFS) and fibromyalgia.

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Twins needed for ME/CFS research

Posted on 01/11/2017 by wames

National ME/FM Action Network announcement:

A senior Canadian researcher has been looking for genetic factors in people with ME/CFS for several years. His studies have already yielded promising results. The next stage of his study involves looking at identical twins where both twins have ME/CFS (“concordant”) or one of the twins has ME/CFS and the other does not (“discordant”). He has already found three sets of identical twins for his study but hopes to find more.

If you are identical twins with discordant or concordant ME/CFS, please contact Margaret Parlor at mefminfo@mefmaction.com to learn more about the study and what it would involve from you.

I am interested in hearing from identical twins affected by ME/CFS anywhere in the world. There are two reasons.

  • Firstly, while this researcher hopes to find enough cases in countries where he has collaborators (Canada, the US and New Zealand), he might need additional cases and might be able to work out suitable arrangements for twins in other locations to participate as well.
  • Secondly, I suspect that other researchers will want to do twin studies. This will give us an indication of how easy or difficult it is to find volunteers and a list of possible volunteers. Please note that if a researcher asks me for names of twins, I will notify you about the study and ask you for permission to share your names; I will not give your names to researchers without notifying you and receiving your permission.

Please share this request widely. And if you know identical twins in this situation, please encourage them to contact me. Thank you!

Margaret Parlor, President, National ME/FM Action Network

mefminfo@mefmaction.com

 

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Differing case definitions point to the need for an accurate diagnosis of ME/CFS

Posted on 01/11/2017 by wames

Research article:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterised by unexplained and persistent or recurrent incapacitating fatigue accompanied by a variety of symptoms and substantial reductions in previous levels of occupational, educational, social and/or personal activity [1,2]. Given the absence of biomarkers for diagnosis, ME/CFS is defined by a combination of symptoms, most of which are non-specific and common to a number of diseases and conditions.

Over 20 case definitions have been proposed, leading to large variations in sensitivity and specificity of diagnosis. These diverse sets of diagnostic criteria and distinct ways in which they have been applied pose significant problems, as research results may vary considerably according to which definition is used. A particular problem occurs when overly inclusive criteria are used, since their lack of specificity may lead to considerable selection bias [3,4].

Unfortunately, many studies, clinical trials in particular, have used broad case definitions such as the Oxford criteria [5], which requires little more than the presence of persistent significant fatigue for over six months and the exclusion of conditions that could explain symptoms, for a diagnosis to be made.

This problem has been highlighted by the Agency for Healthcare Research and Quality (AHRQ) review of evidence for the NIH Pathways to Prevention Workshop [4], which showed significant changes to the interpretation of evidence for treatment, when studies using broad case definitions, such as the Oxford criteria, are excluded from the analysis. The implications for clinical practice suggest that fit-for-all management approaches to ME/CFS, may be inadequate for patients who fulfil better targeted case definitions.

For patients selected using more restrictive definitions, cognitive behavioural therapy (CBT), graded exercise therapy (GET) and other forms of non-drug management approaches to ME/CFS are most appropriate as adjunct therapies rather than restorative treatments, when provided by therapists with a good understanding of ME/CFS. These forms of behavioural intervention have been shown to support the well-being and rehabilitation of those suffering from many chronic and disabling conditions [6]. However, it is very important that the use of behaviourally based management strategies does not deter researchers, physicians and other health professionals from the overarching goal of investigating the causes and pathophysiology of ME/CFS in various sub-groups and the development of specific treatments.

Read more:

Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/ chronic fatigue syndrome by Luis Nacul, Caroline C. Kingdon, Erinna W. Bowman, Hayley Curran & Eliana M. Lacerda in Fatigue: Biomedicine, health & behaviour [Published online 8 Jan 2017]

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Making drugs obsolete: the electroceutical revolution – FM & ME/CFS perspective

Posted on 01/10/2017 by wames

Health rising blog post, by Cort Johnson, 2 Jan 2017: Making Drugs Obsolete: The Electroceutical Revolution – A Fibromyalgia and ME/CFS Perspective

This is the first of three blogs looking at major NIH projects which, while not being aimed at fibromyalgia or chronic fatigue syndrome (ME/CFS), could profoundly affect how they are understood and treated.

The NIH’s Stimulating Peripheral Activity to Relieve Conditions (SPARC) is exploring an entirely new way of treating disease. It proposes to tweak the electrical circuits (nerves) in our bodies to return people to health.

These nerves (every nerve outside the brain and spinal cord) control the health and functioning of every organ in the body. SPARC is slated to spend $250 million over the next seven years in an attempt to learn how to manipulate these nerves to reduce pain, relieve inflammation, heal heart problems, fix gut disorders and more.

Nobody knows if the self-proclaimed “high-risk” project will be successful, but if it is it could usher in a new, side-effect free way of treating illnesses that could put drugs to shame.

The peripheral nervous system is stunningly complex but the general idea is not. It simply consists of using some sort of generator to send electrical impulses down a nerve, causing it to fire. The crude technology used today employs a kind of scattershot approach which ends up activating bunches of nerves.

The “Electroceutical” Revolution?

But with better nerve maps and more refined tools it should be possible to activate just the right fibers in the right nerves to, say, stop some inflammatory processes in their tracks. Or to tweak nerves to fix gut problems, reduce pain, reverse heart failure, or treat diabetes. These are just a few of the possibilities proponents of the electroceutical revolution can envision.

These electroceuticals are either placed on the skin or are surgically implanted where they emit electrical impulses that either fire up or silence nerves. They need not be near the organ of interest at all; one device for patients with bladder problems is placed on the soles of their feet.

Read more about the technology, vagus nerve stimulation and possible effect on reducing inflammation in the ME/CFS immune system

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Fuel shortage: Norwegian study expands on energy problem in ME/CFS

Posted on 01/09/2017 by wames

Health rising blog post, by Cort Johnson, 27 Dec 2016: Fuel shortage: Norwegian study Expands on Energy Problem in Chronic Fatigue Syndrome (ME/CFS)

Fluge and Mella seem to be working at almost lightning speed. Besides managing their huge Rituximab study (and all the sub-studies within it) and the cyclophosphamide trial, they’re also carrying out large research studies.

For years, of course, some researchers and doctors championed the idea that problems with mitochondrial energy production were at the heart of ME/CFS. For many, though, the idea seemed almost too simple…too easy in a way. The body throws too many curves at us for something so obvious to be the cause. But it may be.

The work of Bob Naviaux of UCSD, Ron Davis of the Open Medicine Foundation, McGregor and Armstrong et. al. in Australia, Maureen Hanson at Cornell, and Fluge and Mella in Norway suggest that problems producing energy could, in fact, be causing the physical and mental fatigue in (ME/CFS).

Of course, it’s going to be complex. Exercise studies and other studies have suggested that the aerobic energy production pathways are severely blunted in a significant number of ME/CFS patients. Thus far, though, the metabolomics data suggests that the breakdown comes not in the aerobic energy production pathway but just before it.

Some key facts – such as I understand them.

  • Key Factor in Glycolysis – Pyruvate –  Pyruvate is produced by glycolysis and then gets broken down into acetyl-CoA for use in the mitochondria. When oxygen levels are low, the same process is used to produce ATP anaerobically. Anaerobic energy gets its bad rep because it produces toxins like lactate which build up and cause pain and fatigue. All this occurs in the cell’s cytoplasm.
  • Key Factor in Aerobic Energy Production – Acetyl-CoA – The first goal in aerobic energy production is to produce acetyl-CoA. This occurs in three ways: preferentially by converting pyruvate and/or by converting fatty acids or amino acids. The acetyl-CoA is then broken down further to produce ATP by a process called oxidative phosphorylation. All aerobic energy production occurs in the cell’s mitochondria.

The Study
At 302 patients (200 ME/CFS patients and 102 healthy controls) this was a nice big study. A different type of study than the recent metabolomic studies, it used a mass spectrometer to measure the levels of 20 amino acids involved in energy metabolism in the blood.

QT-RCT PCR was used to examine gene expression. Cells were also cultured, dropped in ME/CFS or healthy control’s serum (blood), tweaked with metabolic factors, and their lactate production and cellular respiration was measured.

Results
Amino Acid Results
Fluge and Mella did a simple but telling thing with the 20 amino acids by dividing them into one of three energy production pathways:

Glycolytic Amino Acids – Amino acids used in the glycolysis pyruvate producing pathway which require PDH to be metabolized (alanine (Ala), cysteine (Cys), glycine (Gly), serine (Ser), and threonine (Thr))

Aerobic Amino Acids – Amino acids that fuel aerobic energy production but which do not require PDH to be broken down((isoleucine (Ile), leucine (Leu), lysine (Lys), phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr)) – mostly ketogenic amino acids

Other Amino Acids – not found in the first category but which are essential to aerobic energy production (anaplerotic – methionine (Met), valine (Val), histidine (His), glutamine (Gln), glutamate (Glu), and proline (Pro), aspartate (Asp), (Asn + Asp = Asx))
Chronic Fatigue Syndrome (ME/CFS) – A Pyruvate Dehydrogenase Disease?

Fluge and Mella found no difference in the levels of the amino acids used in glycolysis – pyruvate production is fine – but reductions in the levels of the ketogenic amino acids used to power aerobic energy production.

Our cells much prefer using glucose to produce energy but the results and the Aussie study suggest that our cells are turning elsewhere.

Remember that our cells – use three different substrates (pyruvate, fatty acids and amino acids) to produce acetyl-CoA but they much prefer glucose.  If pyruvate isn’t being broken down into acetyl-CoA, however, then our cells will turn to another energy source; in this case amino acids. The fact that virtually all the amino acids used to produce acetyl-CoA were depleted in the female ME/CFS patients suggested that their cells, starved of metabolized pyruvate, were turning to and using up amino acids to to produce energy.

Amino acids, unfortunately, are kind of like the body’s last straw for energy production. Our cells would much prefer to use glucose, but even fatty acids are a better source of energy than amino acids. In order for body to use amino acids it has remove an amino group (producing ammonia) and turn them into a sugar.  (The fact ME/CFS patients appear to be turning to amino acids might suggest that they’re having problems with fatty acid metabolism as well.)

There’s another problem, though. If all this unused pyruvate is hanging around, it has to go somewhere. Unused pyruvate gets converted into lactate – a toxin responsible for much of the fatigue and pain associated with exercise. Lactate ultimately gets dumped into the blood stream. Fluge and Mella believe lactate accumulations are probably a key problem in ME/CFS as well. High lactate levels in ME/CFS patients’ brains have been found in several studies but reports on lactate accumulations in the blood are mixed.

Since pyruvate production doesn’t appear to be the problem, the problem must lie in the pyruvate dehydrogenase enzyme complex (PDH) which breaks down pyruvate to produce acetyl-CoA.

Or a Pyruvate Dehydrogenase Kinase Disease?
Fluge and Mella then asked why pyruvate dehydrogenase is not working in ME/CFS and may have found an answer in the increased gene expression (or activity) of the enzymes (PDH kinases (PDK)) that inhibit PDH. Rather encouragingly, they found that increased expression of one form of the PDK enzyme (PDK1) was associated with increased severity and longer duration patients.

Fluge and Mella uncovered numerous irregularities that could be affecting the pyruvate dehydrogenase enzyme in ME/CFS

Digging deeper still they found increased gene expression of the transcription factor (PPAR) which upregulates PDH kinase in ME/CFS patients as well.  Then they discovered that the gene expression levels of another enzyme (SIRT4) that limits pyruvate dehydrogenase production were increased as well.

Things were really humming along; Fluge and Mella’s findings suggested that every step in the chain needed to limit pyruvate dehydrogenase levels were activated in ME/CFS. Their consistently positive findings suggested that an inhibited PDH enzyme really may be a problem in ME/CFS.

Read more about the results of the study

Not just tired: further research suggests cell energy production impaired in ME, by Emily Beardall, 23 Dec 2016 [blog post: A Prescription for M.E. My blog from the intersection of patient & pharmacist]

TV2 interview: New study on pathological mechanisms in ME from researchers in Norway [in Norwegian, subtitles in English]

ME Action blog post: Fluge, Mella and Armstrong: more support for disordered metabolism in ME patients, by Jaime S, 23 Dec 2016

 

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Fatigue & psychosocial variables in autoimmune rheumatic disease & CFS

Posted on 01/06/2017 by wames

Research abstract:

Objective:  Fatigue is common in autoimmune rheumatic diseases (ARD). This study  compared symptom-related cognitions, beliefs, behaviours, quality of sleep, lack of acceptance and distress in participants with ARD such as rheumatoid arthritis (RA), seronegative spondyloarthropathy (SpA), and connective tissue disease (CTD), and participants with chronic fatigue syndrome (CFS).

Methods:  303 participants with RA, SpA, CTD and CFS completed questionnaire  measures of fatigue, social adjustment, cognitive-behavioural responses, lack of acceptance, distress and quality of sleep. The RA, SpA and CTD groups were first compared with each other. They were then combined into one group and compared with the CFS group.

Results:  There were no statistically significant differences between the RA, SpA
or CTD groups for any of the measures. The CFS group was more fatigued, reported more distress and sleep disturbance and had worse social adjustment than the ARD group after adjustment for age and illness duration. After adjustment for fatigue, age, and illness duration, the CFS group scored more highly on lack of acceptance and avoidance/resting
behaviour while the ARD group showed significantly higher levels of catastrophizing, damage beliefs, and symptom focusing than the CFS group.

Conclusion:  Fatigue in rheumatic diseases may be perpetuated by similar underlying transdiagnostic processes. The ARD and CFS groups showed similarities but also key differences in their responses to symptoms. Specific aspects of treatment may need to be tailored towards each group. For example, lack of acceptance and avoidance behaviour may be particularly important in perpetuating fatigue in CFS.

Fatigue and psychosocial variables in autoimmune rheumatic disease and chronic fatigue syndrome: a cross-sectional comparison, by Sheila Ali, Faith Matcham, Katherine Irving, Trudie  Chalder in Journal of Psychosomatic Research, vol 92, Jan 2017 [Available online 14 November 2016]

NB Prof Chalder’s assumption of the existence of avoidance behaviour in CFS was presented in an analysis of the debunked PACE trial results: Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial

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Efficacy of 4-steps physical activity self-regulation programme for chronic fatigue

Posted on 01/05/2017 by wames

Research highlights:

  • 4-STEPS yielded sustained small to moderate sustained effects on self-reported fatigue severity, impact, and health-related quality of life.
  • There were modest effects on physical activity. There were no significant effects on psychological and somatic distress.
  • Benefits on fatigue severity at 12 months were partially explained by physical activity goal progress.

Research abstract:

Objective: Examine the medium-term effects of a brief physical activity (PA) self-regulation (SR) based intervention (4-STEPS program) for chronic fatigue, and explore the mediating effects of PA related variables and SR skills.

Methods: A two-arm randomized controlled trial (Usual Care vs 4-STEPS) was carried out. The 4-STEPS program consisted of Motivational Interviewing and SR-skills training. Fatigue severity (primary outcome) and impact, PA, health-related quality of life (HrQoL), and somatic and psychological distress were assessed at baseline, post-treatment (12 weeks) and 12 months follow-up.

Results: Ninety-one patients (45 intervention and 46 controls) were included. At follow-up, there were significant treatment effects on fatigue severity (g = 0.72) and fatigue impact, leisure-time PA, and physical and psychological HrQoL. No significant effects were found for number of daily steps and somatic and psychological distress.

Fatigue severity at follow-up was partially mediated by post-treatment progress on a personal PA goal (effect ratio = 18%).

Conclusion: Results suggest that a brief intervention, focusing on the formulation and pursuit of personal PA goals and the use of SR skills, produces sustained benefits for fatigue severity. Despite these promising results, dropout was high and the intervention was not beneficial for all secondary outcomes.

Efficacy of a randomized controlled brief physical activity self-regulation intervention for chronic fatigue: Mediation effects of physical activity progress and self-regulation skills, by MM. Marques, V De Gucht, I. Leal, S. Maes in Journal of Psychosomatic research, [Published online: December 26, 2016]

 

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Metabolic profiling reveals disturbances in fatty acid & lipid metabolism in ME/CFS

Posted on 01/05/2017 by wames

Research abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a continuum spectrum disease without biomarkers or simple objective tests, and therefore relies on a diagnosis from a set of symptoms to link the assortment of brain and body disorders to ME/CFS. Although recent studies show various affected pathways, the underlying basis of ME/CFS has yet to be established.

In this pilot study, we compare plasma metabolic signatures in a discovery cohort, 17 patients and 15 matched controls, and explore potential metabolic perturbations as the aftermath of the complex interactions between genes, transcripts and proteins.

This approach to examine the complex array of symptoms and underlying foundation of ME/CFS revealed 74 differentially accumulating metabolites, out of 361 (P<0.05), and 35 significantly altered after statistical correction (Q<0.15). The latter list includes several essential energy-related compounds which could theoretically be linked to the general lack of energy observed in ME/CFS patients.

Pathway analysis points to a few pathways with high impact and therefore potential disturbances in patients, mainly taurine metabolism and glycerophospholipid metabolism, combined with primary bile acid metabolism, as well as glyoxylate and dicarboxylate metabolism and a few other pathways, all involved broadly in fatty acid metabolism.

Purines, including ADP and ATP, pyrimidines and several amino acid metabolic pathways were found to be significantly disturbed. Finally, glucose and oxaloacetate were two main metabolites affected that have a major effect on sugar and energy levels. Our work provides a prospective path for diagnosis and understanding of underlying mechanisms of ME/CFS.

Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism by Arnaud Germain, David Ruppert, Susan M Levine and Maureen R Hanson in Mol. BioSyst. [First published online 23 Dec 2016]

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Poor sleep quality, greater circulating pro-inflammatory cytokines & severity & frequency of CFS/ME

Posted on 01/04/2017 by wames

Research highlights:

  • Sleep quality, inflammation, and CFS/ME symptoms were analyzed.
  • Poor sleep quality predicted pro-inflammatory cytokines IL-1β, IL-6, and TNF-α.
  • Worse sleep quality related to greater fatigue severity and daily interference.
  • Worse sleep quality related to more severe and frequent CFS/ME symptoms.
  • Further research is needed to identify the etiology of sleep disruptions in CFS/ME.

Research abstract:
Objective
Poor sleep quality has been linked to inflammatory processes and worse disease outcomes in the context of many chronic illnesses, but less is known in conditions such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms.

Methods
Sixty women diagnosed with CFS/ME were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Symptom Inventory (FSI) and Center for Disease Control and Prevention (CDC)-based CFS/ME symptom questionnaires. Circulating plasma pro-inflammatory cytokine levels were measured by ELISA. Multiple regression analyses examined associations between sleep, cytokines and symptoms, controlling for age, education, and body mass index.

Results
Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β) (β = 0.258, p = 0.043), IL-6 (β = 0.281, p = 0.033), and tumor necrosis factor-alpha (TNF-α) (β = 0.263, p = 0.044). Worse sleep quality related to greater fatigue severity (β = 0.395, p = 0.003) and fatigue-related interference with daily activities (β = 0.464, p < 0.001), and more severe and frequent CDC-defined core CFS/ME symptoms (β = 0.499, p < 0.001, and β = 0.556, p < 0.001, respectively).

Conclusions
Results underscore the importance of managing sleep-related difficulties in this patient population. Further research is needed to identify the etiology of sleep disruptions in CFS/ME and mechanistic factors linking sleep quality to symptom severity and inflammatory processes.

Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women by Sara F. Milrad, Daniel L. Hall, Devika R. Jutagir, Emily G. Lattie, Gail H. Ironson, William Wohlgemuth, Maria Vera Nunez, Lina Garcia, Sara J. Czaja, Dolores M. Perdomo, Mary Ann Fletcher, Nancy Klimas, Michael H. Antoni in Journal of Neuroimmunology, 13 December 2016.

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