Fecal metagenomic profiles in subgroups of patients with ME/CFS

[Marco]

Compared to controls typical markers for inflammation are often elevated in ME/CFS patients (CRP, IL-6, neopterin etc..). It's not that these patient groups don't have elevated markers for inflammation, rather that they cannot identify a consistent pattern.

I'd like to see more emphasis on individual patient measures than group differences. I suspect sub-groups are masking many potential significant differences from controls.

 

[Marco]

This paper I referenced earlier in the thread http://forums.phoenixrising.me/inde...patients-with-me-cfs.51002/page-5#post-842084 suggests that endurance exercise results in (both negative and positive) alterations to the microbiome affecting some of the species mentioned in the Hornig paper.

By implication the differences seen in the ME/CFS microbiome could be due to inactivity. Ideally they would need to exclude that possibility.

 

[Kati]

I'd like to see more emphasis on individual patient measures than group differences. I suspect sub-groups are masking many potential significant differences from controls.

And then there would need to be hundreds if not thousands of patients to add to statistical power to what we all have in common (test wise, not symptom wise) and tease out the subsets.


We always seem to be limited by money.

 

[Marco]

And then there would need to be hundreds if not thousands of patients to add to statistical power to what we all have in common (test wise, not symptom wise) and tease out the subsets.


We always seem to be limited by money.

I was thinking more in terms of examining individual data sets to see if there are any unusual patterns. It may be that in some individuals certain measures are elevated and in others lowered. In a straight group comparison the two 'sub-groups' would cancel each other out.

 

[justy]

Sorry to have to ask, but in my understanding it's a huge difference between, on one hand, free LPS that may be dissolved in the intestinal fluids and get squeezed through thin gaps of the intestinal wall, when too many tight junctions have given up, resulting in a gap between the epithelial cells, and on the other hand whole bacteria, that ends up outside of the intestin, in the tissues, gets into the lympatic system, and possibly into the blood stream.

Without doing the math, I think the dimensions of the gap that bacterias can pass through must be magnitudes larger that that kind of gaps that LPS may get filtered through.

Sorry not sure what you are asking, don't know much about what you are discussing - sounds feasible. WHat I am talking about is PROVEN traslocation - bacteria that should not be there showing in the blood. This is what I have.

 

[ash0787]

my concerns -

how does this tie into multiple onset triggers ? how fast could a stomach ecosystem change which is extensive enough to cause disease causing change take place ?

by what possible mechanism could this tie into rons discovery ? could there be some sort of toxin these bacteria are producing which can disrupt the metabolism of the individual muscle cells in such a way ?

could such a scenario persist despite varying patient lifestyles including starvation and even targeted interventions aimed at the stomach ?

 

[Manganus]

Sorry not sure what you are asking, don't know much about what you are discussing - sounds feasible. WHat I am talking about is PROVEN traslocation - bacteria that should not be there showing in the blood. This is what I have.

Are these lipopolysaccharids anchored on living bacteria, or are they assumed to be free proteins in the intestinal fluid?

Those lipopolysaccharids that are argued to trigger not only an innate immune response, but also argued to cause gaps in the endothelial wall.

That's what I try to understand.

 

[AndyPR]

The Virology blog, of David Tuller and open letters about PACE fame, has covered this study, http://www.virology.ws/2017/04/27/intestinal-dysbiosis-in-mecfs-patients/

 

[bertiedog]

Cort writes that Lipkin will be publishing a follow-up study shortly which will discuss possible treatments -

http://simmaronresearch.com/2017/04/chronic-fatigue-syndrome-microbiome-gut-subset/#comment-16973

It would seem that Dr Lipkin thinks that there will be two distinct treatments that might be helpful if ME/CFS patients do indeed shows the problems mentioned in the study discussed above. One involves drugs that modulate the immune response whereas the other will benefit sufferers with drugs that modulate neurotransmitters.

I find this very interesting because I definitely fit the picture having had Campylabactor poisoning in 1998 and being unable to work by 2000. My Genova GI effects stool test done late 2015 are typical of Lipkin's findings with low abundance of the beneficial bacteria despite a good high fibre diet and me having taken lots of good probiotics.

Pam

 

[ljimbo423]

A general question: how can LPS in plasma make you feel ill if there is no cytokine/C4a/CD14 response?

They have found both high and low cytokine levels in cfs. They found high levels of some cytokines in cfs patients of 3 years or less (short duration) and low levels of the same cytokines in patients with long duration of illness, greater than 3 years. Taken as a whole, which most studies have done, they would cancel each other out. Showing the same cytokines, as neither high nor low, but in the normal range.

“It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop,”

LINK

 

[Kati]

I was thinking more in terms of examining individual data sets to see if there are any unusual patterns. It may be that in some individuals certain measures are elevated and in others lowered. In a straight group comparison the two 'sub-groups' would cancel each other out.

I agree and I understood but I also think that bigger samples are needed to truly understand our heterogenous patient population.

 

[cigana]

They have found both high and low cytokine levels in cfs. They found high levels of some cytokines in cfs patients of 3 years or less (short duration) and low levels of the same cytokines in patients with long duration of illness, greater than 3 years. Taken as a whole, which most studies have done, they would cancel each other out. Showing the same cytokines, as neither high nor low, but in the normal range.

LINK

But that doesn't explain how we can have symptoms without cytokines...

 

[RogerBlack]

But that doesn't explain how we can have symptoms without cytokines...

I'm waiting for someone to blame midochlorians.

 

[Solstice]

I'm waiting for someone to blame midochlorians.

Whoever thought those up should be court-marshalled..

 

[Valentijn]

I'm waiting for someone to blame midochlorians.

Well, there is a bacteria named after them which can infect the mitochondria I know of at least one ME patient who has tested positive at a lab in a German university.

 

[Manganus]

Well, there is a bacteria named after them which can infect the mitochondria I know of at least one ME patient who has tested positive at a lab in a German university.

Hey, Valentijn!
That was interesting.

(In a general scientifical sense, I mean.)

But then... who the heck were the midochlorians?

 

[Valentijn]

But then... who the heck were the midochlorians?

The pseudo-explanation for Jedi powers, created in Episode I of Star Wars.

 

[Solstice]

The pseudo-explanation for Jedi powers, created in Episode I of Star Wars.

AKA the worst thing to happen to the franchise, that episode one.

To stay on topic, I wonder if filgotinib could "break the chain" as they say, in the future. Stop LPS/inflammation then our immune system returns to normal and our gut resets too. I'm a layman though, so half the stuff posted in this forum is way over my head.

 

[FMMM1]

Hi, from memory Chris Armstrong (Melbourne University) proposed that switching to burning amino acids as an energy source (rather than glucose) would lead to a less acidic gut with consequent switch in gut bugs (to a pro-inflamatory microbiome). Check out his 2016 webinar and subsequent publication. Interestingly, Chris suggested that once you've the disrupted metabolism (burning protein rather than glucose) then you get the disrupted microbiome which maintains the disrupted metabolism (viscous circle).

Also, folks at the IMO (Ron Davis among others) have been looking for something in plasma which is switching the cellular metabolism (from burning glucose to amino acids - I assume) - there's a recent video online, and blogs on this site, covering this . Finding that would appear to be interesting; since turning it off would presumably allow the microbiome to return to normal.

PS - I think someone suggested that Davis's team first identified the metabolic switch to burning amino acids. I'm pretty sure it was Chris Armstrong (among others); however, the paper just didn't get picked up until the publication by Davis's team regarding altered metabolism in ME/CFS. Check out the webinar.

Good to see this gut bugs paper but when are we going to see the diagnostic tested mentioned here? Also, is the bug test expensive i.e. if it could be used to diagnose?

Sorry for the rushed email.

From a brief scan it seems that some of the intestinal bacterial species that were seen to be increased are associated with the following:

- Increased fermentation
- Glucose tolerance/metabolism

Now i'm no expert but we already know from Davis/Fluge & Mella that there's something wrong with energy production and we seem to be falling back on the less efficient methods. Would it not make sense then to see increases in these bacterial species if we're having to rely on anaerobic respiration/fermentation more? To me it seems like changes in the microbiome could be a consequence rather than a cause of ME. I'm definitely interested to hear logical arguments as to why I could be wrong though!

 

[Barry53]

Up to 90 percent of ME/CFS patients also have IBS.

This is very interesting. My wife does not have IBS, but there are common foods we have learned she must avoid, else she does end up with severe stomach/gut issues ... if she indulged in some foods she would have persistent IBS-like symptoms, and in some cases become very ill indeed. Homing in on what foods need avoiding is actually very very tricky, and I suspect that many/some of the ME/CFS sufferers presenting with co-morbid IBS, could in fact be people who have not identified the foods they need to avoid or be very careful about. Ordinary, normally good, foods such as:-

Bananas
Tomatoes
Sweet peppers
Chilli peppers
Soya

So I wonder here if the 10% are people who have the potential for IBS, but have learned what foods they need to avoid?