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Altered microbiome composition in individuals with fibromyalgia, 2019, Minerbi et al.

Discussion in ''Conditions related to ME/CFS' news and research' started by MeSci, Jun 21, 2019.

  1. MeSci

    MeSci Senior Member (Voting Rights)

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    This is a report on the research - I think that the paper can be accessed from it.

    Source: McGill University Health Centre

    Datd: June 19, 2019

    URL:
    https://muhc.ca/newsroom/news/gut-bacteria-associated-chronic-pain-first-time

    Ref:
    https://journals.lww.com/pain/Abstr...me_composition_in_individuals_with.98647.aspx

    Gut bacteria associated with chronic widespread pain for first time
    ---------------------------------------------------------
    People with fibromyalgia show variations in microbiome composition

    Scientists have found a correlation between a disease involving chronic pain and alterations in the gut microbiome.

    Fibromyalgia affects 2-4 percent of the population and has no known cure. Symptoms include fatigue, impaired sleep and cognitive difficulties, but the disease is most clearly characterized by widespread chronic pain. In a paper published today in the journal Pain, a Montreal-based research team has shown, for the first time, that there are alterations in the bacteria in the gastrointestinal tracts of people with fibromyalgia. Approximately 20 different species of bacteria were found in either greater or are lesser quantities in the microbiomes of participants suffering from the disease than in the healthy control group.
     
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  2. InitialConditions

    InitialConditions Senior Member (Voting Rights)

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    I imagine the gut microbiome correlates with any significant change in bodily systems. The key question of course is: is there a causal connection?
     
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  3. Patient4Life

    Patient4Life Senior Member (Voting Rights)

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    My sister asked me to try a pro-biotic. She said not that it can resolve FM or ME/CFS but maybe my IBS and might get some sort of immune system support and that it was being said emotions and so on are impacted by gut bacteria. So, I tried it and right away my IBS is better and I don't have to take a peppermint gel in the morning or use a Beano type generic.

    I do feel better emotionally, too. And, my brain isn't hurting as much (not headaches or migraines, actually the whole parameter would hurt) and it hasn't burned since I started it which would happen once or twice a week.

    Taking a prebiotic with it.
     
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  4. DokaGirl

    DokaGirl Senior Member (Voting Rights)

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    This is an exciting article. The altered gut bacteria may not be causing Fibro, but at least researchers have found this physiological abnormality. Would be great if they would check out pwME too. That would add to the studies others are doing for ME and the microbiome. Nonetheless, it's heartening to see these results. I hope they get funding to carry on.
     
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  5. rvallee

    rvallee Senior Member (Voting Rights)

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    At the point we're at, correlation is still good if it is reliable and replicable. If only for the purpose of a test. When you're still shackled to the starting line, every step forward counts.
     
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  6. Hutan

    Hutan Moderator Staff Member

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    I was a bit underwhelmed by this as there's maybe 1000 species of bacteria in the gut microbiome, so odds were that there'd be plenty that happened to be in greater or lesser quantities than in the microbiomes of controls. But the finding does seem a bit more robust than that.

    Abstract:
    Fibromyalgia (FM) is a prevalent syndrome, characterised by chronic widespread pain, fatigue and impaired sleep, that is challenging to diagnose and difficult to treat. The microbiomes of 77 women with FM and that of 79 control participants were compared using 16S rRNA gene amplification and whole genome sequencing. When comparing FM patients to unrelated controls using differential abundance analysis, significant differences were revealed in several bacterial taxa.

    Variance in the composition of the microbiomes was explained by FM-related variables more than by any other innate or environmental variable and correlated with clinical indices of FM.
    In line with observed alteration in butyrate metabolising species, targeted serum metabolite analysis verified differences in the serum levels of butyrate and propionate in FM patients.

    Using machine learning algorithms, the microbiomecomposition alone allowed for the classification of patients and controls (ROC AUC 87.8%). To the best of our knowledge, this is the first demonstration of gut microbiome alteration in non-visceral pain. This observation paves the way for further studies, elucidating the pathophysiology of FM, developing diagnostic aids and possibly allowing for new treatment modalities to be explored.

    I haven't read the full article but it is open-access.
     
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  7. Hutan

    Hutan Moderator Staff Member

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    Yes.

    This 2016 paper from Maureen Hanson's team found lower levels of bacteria that produce butyrate in a ME/CFS cohort and note IBD and IBS research finding the same. That IBD and IBS research also found lower levels of butyrate in the gut, corresponding to the lower levels of the butyrate-producing bacteria.

    Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome

    I don't know what later ME/CFS studies have found.
     
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  8. Hutan

    Hutan Moderator Staff Member

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    https://www.ncbi.nlm.nih.gov/pubmed/29986139
    Dietary Fiber Increases Butyrate-Producing Bacteria and Improves the Growth Performance of Weaned Piglets.
    :)

    The study investigated the impact of dietary fibers on the performance, fecal short-chain fatty acids, nutrient digestibility, and bacterial community in weaned piglets with the control group (CON) and dietary supplementation of 5% corn bran (CB), 5% wheat bran (WB), or 5% soybean hulls (SB). The piglets in CB and WB groups showed greater weight gain and feed efficiency ( p < 0.05) in comparison to piglets in CON and SB groups.

    Fecal samples from piglets in CB, SB, and WB groups contained greater ( p < 0.05) butyrate levels than fecal samples from piglets in the CON group. The fecal samples from piglets in CB or WB groups contained greater ( p < 0.05) abundances of Actinobacteria and Firmicutes or Fibrobacteres than the fecal sample from piglets in the CON group, which could promote fiber degradation and the production of butyrate.

    In summary, dietary CB or WB may enhance the growth performance of weaned piglets via altering gut microbiota and improving butyrate production, which shed light on the mechanism of dietary fiber in improving gut health.
    I'm off to eat some celery.
     
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  9. DokaGirl

    DokaGirl Senior Member (Voting Rights)

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    @Hutan, thank you for all this info. Yes.....fibre!

    The BPS model of IBS being psychosomatic is crap! Ha!
     
  10. Hutan

    Hutan Moderator Staff Member

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    Ha, I should have learned by now to not just read the abstract. I was a bit concerned that the abstract didn't actually say whether the butyrate producing bacteria and the butyrate levels were up or down. Here's the relevant section:

    Consistent alterations in the abundance of butyrate-metabolism-related bacteria were observed:F. prausnitzii and B. uniformis were found in lower relative abundance in FM patients, while higher relative abundance was observed for Intestinimonas butyriciproducens, Flavonifractor plautii, Butyricoccus desmolans, Eisenbergiella tayi and Eisenbergiella massiliensis.

    To explore the possible metabolic effect of these alterations, a targeted metabolite approach was used to measure the serum concentrations of butyric acid, isobutyric acid, propionic acid and lactic acid.

    Serum levels of butyric acid in FM patients (n=73) were higher compared to unrelated controls (n=46, p=0.005), while levels of propionic acid were lower (p=0.006) and a trend towards lower levels of isobutyric acid was also observed (p=0.056). No significant differences in the serum levels of lactic acid was observed (Figure 4B). Multivariate analysis showed a significant between-group difference (Pillai’s Trace, F=8.97, p<0.0001).
    So FM patients actually had higher levels of butyric acid in their serum, with just a trend to lower levels of isobutyric acid. And levels of butyrate-metabolism-related bacteria were a bit all over the place at the species level. And there was no difference in the fibre-intake between the FM cohort and the controls.

    As usual, it seems that it's complicated...


    When considering the nineteen specific species identified as significantly differentially abundant between FM patients and unrelated control participants, there was a broad range in how well- characterised these species were. Those species putatively depleted (lower in relative abundance) in FM were relatively well-characterised and included Faecalibacterium prausnitzii, Bacteroides uniformis, Prevotella copri and Blautia faecis.

    Faecalibacterium prausnitzii is one of the most abundant and well-studied butyrate producing bacteria in the human gut [46]. This species has been reported to be depleted in multiple intestinal diseases and was therefore suggested as a potential marker for gut disorders. Within the gut, F. prausnitzii has been reported to exert anti- nociceptive as well as anti-inflammatory effects [58,79] and to enhance the intestinal barrier function [46]. Similar to our observations, F. prausnitzii was also reported to be depleted in patients with CFS [61].

    Bacteroides uniformis, is one of several species which have recently been reported as having altered relative abundance in patients with inflammatory arthritis, along with H. parainfluenza,P. copri and others [96]. B. uniformis and H. parainfluenza were detected in synovial tissues of osteoarthritic joints, whereas P. copri and H. parainfluenza were detected in rheumatoid arthritis synovial fluid. P. copri is thought to mediate inflammatory response via Th17 activation [37,43], and was also shown to induce arthritis in an animal model of arthritis-prone mice [51]. In this study, these species were found in lower abundance in FM patients. Although FM is often considered to be a rheumatologic disease, it seems that at least some species previously found at higher abundance in inflammatory rheumatic diseases are depleted in FM.​

    In contrast to the depletion of butyrate producers F. prausnitzii and B. uniformis in FM patients, we observed significant higher relative abundance of a number of other known intestinal butyrate producers: Intestinimonas butyriciproducens, Flavonifractor plautii, Butyricoccus desmolans,Eisenbergiella tayi and the recently identified Eisenbergiella massiliensis . Alterations in butyrate and propionate metabolizing species were further supported by alterations in serum levels of these short chain fatty acids. Coherent with this putative shift in the butyrate producing community of FM patients, Parabacteroides merdae was also significantly higher in relative abundance in FM patients.

    Recently, P. merdae has been reported by Olson et al. to be one of two key mediators of the anti-epileptic effect of the ketogenic diet [64]: in a mouse model, ketogenic diet can drive an increase in the abundance of P. merdae, which in turn, by regulation of amino acid γ-glutamylation leads to an increase in hippocampal γ-aminobutyric acid (GABA)/glutamate ratio. The increase in the inhibitory to excitatory neurotransmitter ratio in the brain is thought to protect against seizures. The second key mediator species of the ketogenic diet effect on seizures reported by Olson et al. was Akkermansia muciniphila, which in our cohort was also found at higher abundance in FM patients, although this observation did not reach statistical significance (p=0.042, Benjamini-Hochberg FDR=0.27).​

    It's interesting stuff, although clearly early days.

    The study looks to have been well done as far as a quick skim by someone unqualified to judge can tell. Canadian researchers. Perhaps worth encouraging them.
     
  11. Hutan

    Hutan Moderator Staff Member

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    So this study of FM patients found Faecalibacterium prausnitzii to be depleted. And they reference a 1979 study that found lower levels of F. prausnitzii in people with CFS.

    They don't reference the much more recent Hanson study (mentioned above) that found the same thing.

    I wonder if the two research groups are aware of each other.
     
    Last edited: Jun 22, 2019
  12. arewenearlythereyet

    arewenearlythereyet Senior Member (Voting Rights)

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    Like with all these things it will need a lot more research and a lot more power in terms of number of studies (for all sorts of conditions and circumstances) to understand the significance of the result.

    It’s good that we have some species level findings in this study, however as an observation it doesn’t tell us very much without fully understanding the context.

    It’s like finding a gene mutation before you have mapped the full genome/ invented gene therapy techniques/understand the prevalence and significance and relevance to the various illnesses. Partly useful but you are still in the dark in terms of significance in the wider context or actually what to do about it. To further extend this comparison...imagine our understanding of gene therapy from a perspective of the 1940’s/50’s.

    An example for further study would be diet variance. Different cultures eat quite vastly different diets ...what is the impact here, is there selection bias based from the cohort chosen (77 people with fibro, 79 controls, many from the same family)? What is the impact of controls with similar fibre but with other conditions from other cultures? What about high and low fibre controls? We are told that they conclude that the control eliminates diet ..but I’m not sure such a sweeping statement can really be made when you don’t understand the intricacies of diet in the first place?

    This could easily be an unrelated artefact from the study or one that in practice is so downstream that it has no bearing on the condition whatsoever?

    The researchers do however recognise this and say
    However we also have the tricky element of strains (subset of species). There are hundreds of strains of E.coli for instance and only a small subset of these are harmful to humans. We may need to understand things at a much more granular level than even species to understand significance if strains are behaving in such polar opposite ways in terms of their influencing symptoms (if indeed that is what they are actually doing)

    So interesting but very very early days. We will need more studies across very many variables to fully understand context.
     
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  13. rvallee

    rvallee Senior Member (Voting Rights)

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    We can say the same of amyloid plaques in Alzheimer's disease or demyelination in MS. Are they cause or consequence? All we know is they are relevant. Every small step counts if it's significant. But there is definitely a growing body of evidence for the role of gut bacteria in many diseases, way more than most still suspect. I'd say this adds up to more than minor significance. When things align independently, it reinforces individual findings.

    It shouldn't be that surprising that the thing that provides most nutrients to our bodies would be significant, but somehow it's still fashionable to believe that there are things in human biology that serve little to no purpose or have very little effect on the whole, which is frankly weird. Like "junk DNA", it's such a weird opinion to assume that what we don't understand is likely useless.
     
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  14. DokaGirl

    DokaGirl Senior Member (Voting Rights)

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    Further to my earlier comment about this being an exciting study - very little to zero biomedical research on ME or Fibro ever happens in Canada. Seeing that something had, even though preliminary, was quite heartening. Some advocates would of course say I'm happy with accepting this crumb. Nonetheless, it's still encouraging to see this research in Canada, which has been a biomedical wasteland for ME and FM for far too long.

    A great deal more funding is very much needed to investigate the microbiome. Researchers are looking at it from different disease view points, and I hope they're collaborating. There is a CBC TV program, The Nature of Things that discussed the microbiome, autism, and diets in various cultures. I'll see if I can find the link later, when I'm more up and about.

    @rvallee, it's a similar attitude - what the powers that be don't understand is useless, or what they can't explain should be relegated to the psychological realm, as ME has been.
     
    Last edited: Jun 23, 2019
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  15. DokaGirl

    DokaGirl Senior Member (Voting Rights)

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    Youtube link to The Autism Enigma. UK, Canadian and US researchers interviewed re gut bugs and their research. I hope that many researchers who are working on the human microbiome from different view points are collaborating:

    https://www.youtube.com/watch?v=53yzwWsBeAc




    Not sure how to just show the link, as the program kicks right in without showing the link. Will try again later.

    I have reported this problem to the moderators. In the meantime, this may be of interest re gut bugs, and disease. Some interesting discussion and studies noted on this program.
     
    Last edited: Jun 23, 2019
  16. shak8

    shak8 Senior Member (Voting Rights)

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    I dropped out (never sent in specimens) out of Harvard's Nurses Health Study of gut microbiome in a cohort of nurses. They did have a dietary recall element of test (which I found quite unreliable and complained in the past as to its accuracy, but they assured me that it is okay). So at least there they are studying the microbiome and have dietary data for their specimens collected.

    But my test was dietary focused, I believe. Not any specific illness, although they did collect your DNA swab as well.

    As in so much research, a lot of bits and pieces and some of the pieces lack scientific rigor.
     
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