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Reduced diversity and altered composition of the gut microbiome in individuals with ME/CFS

Discussion in 'Latest ME/CFS Research' started by Kyla, Jun 23, 2016.

  1. Kyla

    Kyla ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ

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    https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4
    (Open access)

     
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  2. aimossy

    aimossy Senior Member

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  3. msf

    msf Senior Member

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    Ooh, we didn´t have to wait long!

    On KDM and Maes´ MP3s today: The Hives - Hate to Say I Told You So.
     
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  4. msf

    msf Senior Member

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    Ah, as I expected, they only used the Fukuda criteria - does this make KDM´s study (see thread on IiME conference) more relevant for people with ME then?
     
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  5. msf

    msf Senior Member

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    Ah, as I expected, they only used the Fukuda criteria - does this make KDM´s study (see thread on IiME conference) more relevant for people with ME then?

    ´ME/CFS patients had significantly higher plasma LPS levels than healthy individuals (median ME/CFS—119.43 pg/mL vs. controls—74.74 pg/mL, P < 0.0005´ - please tell me someone isn´t going to say this isn´t valid because they didn´t correct for multiple comparisons.
     
  6. msf

    msf Senior Member

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    Looks like technology may have advanced since the KDM study, or the KDM group didn´t choose the best tool for the job:

    ´Recently, a study used high-throughput 16S rRNA gene sequencing to investigate the presence of specific alterations in the gut microbiota of ME/CFS patients from Belgium and Norway [12]. The authors amplified the V5 and V6 hypervariable 16S rRNA regions and sequenced the amplicons using a Roche FLX 454 sequencer, which resulted in an average of only 6000–7000 reads/sample. In contrast, we amplified the V4 hypervariable region of the 16S rRNA gene, sequenced amplicons using the MiSeq Illumina platform, obtained an average of many more reads/sample (98,000), and compared the resulting sequences to a different database, the Greengenes non-redundant reference database [31]. Our analysis showed that within-sample diversity is lower in the ME/CFS specimens compared to controls.The same indices in the Fremont et al. [12] study did not differ between ME/CFS and healthy subjects [12], likely due to the lower read number they obtained. Lower richness has also been observed in unhealthy or inflammatory states [32, 33] and has been associated with IBD, necrotizing enterocolitis [34], and greater abdominal discomfort levels in patients with food intolerances [35, 36].´
     
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  7. A.B.

    A.B. Senior Member

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    I'm not qualified but I believe the very low p value makes it unlikely for this to be due to chance. Maybe someone who knows more about correcting for multiple comparisons can weigh in.
     
  8. msf

    msf Senior Member

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    I was (hopefully) being sarcastic. They seem to have corrected for numerous comparisons later in the paper, but whether it is relevant to the LPS measurement I cannot say.
     
  9. Bob

    Bob

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    Mark's blog says that Maureen Hanson mentioned this at the Invest in ME conference. And she says they are aiming to get 100% accuracy.
    I haven't read the paper yet.
     
    Last edited: Jun 24, 2016
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  10. Snow Leopard

    Snow Leopard Hibernating

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    Interesting... Also given I just got my uBiome results today.
     
  11. msf

    msf Senior Member

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    I remember Fluge and Mella referenced Maes in one of their papers, but I can´t remember which paper they referenced. I would be interested to hear their take on this.
     
  12. A.B.

    A.B. Senior Member

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    Anyone want to show their results? My metagenomics stool analysis (through Red Labs):

    Fimicutes were 49%, normal would be 50-85% in Europeans. The test indicated that I have low diversity. My sCD1 was also high, but just barely. Seems loosely in line with the findings here.
     
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  13. msf

    msf Senior Member

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    Yeah, almost all of the KDM patient results I have seen are in line with the findings in this study.

    I´ll find and post my results later.
     
    Last edited: Jun 24, 2016
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  14. Thinktank

    Thinktank Senior Member

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    The findings correlate with my own testing;

    Low firmicutes / low bifido / high bacteroides / low diversity
    Very high sCD14
     
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  15. sarah darwins

    sarah darwins I told you I was ill

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    Same kind of thing. Borderline firmicutes, zero bifido, high bacteroides, high (slightly) sCD14.
     
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  16. user9876

    user9876 Senior Member

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    I think we need to be careful with P values. What they basically say is that the chance that the measures come from the same distribution are small (in this case). However, the distributions can be overlapping which means that the measure is not a good bio marker and I would go further and say that this measure is clearly not the cause. It could be part of the cause but since the distributions overlap there are healthy people with the same levels as people with ME. Hence we need to do more to understand what the role of this and the other measures could be within the overall system. It could for example be an issue of this and genes or multiple different measures together.

    This suggests something interesting particularly if there are subsets. However, in a very quick skim through their paper I'm not sure what methodology they used. Really they should have three data sets the first to train several classifiers, the second to choose what appears to be the best classifier (test set) and a third to test the performance of the overall classifier (verification set). Without this the classification results could be over stated.

    What I would like to see is a clustering over all the variables they collect to see if there are clear clusters or ones representing different subgroups.

    I say all this with no understanding of the anything about the biology of the situation and as such these are general comments about data and overlapping groups.
     
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  17. A.B.

    A.B. Senior Member

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    My bacteroides were low, but my bifidobacteria were very high. sIgA (not measured in this study) was extremely high and the most unusual of all tested things. So the bacteroides/bifido findings don't match my results, but the firmicutes/sCD14 do.
     
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  18. msf

    msf Senior Member

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    I think you will find that it is the cause of most of the general ME symptoms. What you are going to see next is the same study done in people with ME who have just done exercise, and there is going to be even clearer difference between cases and controls.

    Also, you need to remember that they used Fukuda, so they will have included patients who do not have ME but some other condition, most likely one that doesn´t show increased levels of plasma LPS.
     
    Last edited: Jun 24, 2016
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  19. Simon

    Simon

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    Yes, while they don't seem to have corrected for multiple comparisons, this p value would survive it, especially as most of the measures are, unsurprisingly, highly correlated (LPS, LBP ie LPS-binding protein, and sCCD14, which is activated by LPB). This means using eg Bonferroni correction would be too strict ie even easier for that p value to survive correction for multiple comparisons. However, as @user9876 says, the levels overlap substantially between patients and controls, making it a quesitonable biomarker. Looking at the data, there seem to be signs of subgroups - maybe a biomarker for a subgroup?

    See my edit of Figure 1 (nb order in my edit is d, b, e)
    hansonlps.png

    Agreed, though they used random forest for classification and also used cross--validation, both of which should reduce overfitting (and false positives). Even so, needs replication.
     
    Last edited: Jun 24, 2016
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  20. A.B.

    A.B. Senior Member

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    Do you mean the way LPS clusters in Figure 1? In patients, it's either below average or above average but few have "average" LPS.
     
    Simon likes this.

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