Fecal metagenomic profiles in subgroups of patients with ME/CFS

[AndyPR]

I think you mean that they have a theory that leaky gut cause inflammation. That's it. They aren't speculating that the issues with the gut are causing ME, which seems to be what you are trying to imply.

 

[ljimbo423]

Xifaxin seemed to help this person somewhat.

I spent years trying to get up to a therapeutic dose of antibiotic herbs and I couldn't because the bacteria that was being killed off (die-off), in my gut, caused flares in my symptoms that I could not tolerate. I believe the die-off is from the lipopolysaccharides (LPS) in the cell walls of gram negative bacteria in my gut, being killed off and the LPS pass through an over-permeable gut (leaky gut).

It took me 4 months to get up to a very small dose of antibiotic herbs, with a lot of die off along the way. I then took a 10 day course of Rifaximin at 1200mg a day and was able to go up to 15-20 times the dose of antibiotic herbs, in just a month or so, with very little die off or symptom flares. So the connection of symptoms and high dysbiotic gut bacteria, for me, is clear.

Rifaximin only works in the small intestine and is not absorbed into the blood stream. So the improvements I made were from lowing the bacterial overgrowth in my small intestine.

These interventions have greatly improved my level of physical functioning and my well being, profoundly, along with a starch free diet and high dose probiotics. I haven't felt this good in many years. I am certain my symptoms are directly connected to the level of dysbiotic bacteria in my gut.

If I want to worsen my symptoms, all I have to do is take too high a dose of berberine, oil of oregano etc. A high enough dose would put me in bed I'd be suffering so much and I rarely even take naps now. I firmly believe that Lipkin, Hornig, Chris Armstrong and others will, in time, show that the gut is the core issue.

 

[Marco]

I think you mean that they have a theory that leaky gut cause inflammation. That's it. They aren't speculating that the issues with the gut are causing ME, which seems to be what you are trying to imply.

If that's all their theory involves why use a ME/CFS population and why did you (and I) crowd-fund it?

 

[arewenearlythereyet]

Weaned piglets E-coli can kill whole litters.

It can also be quite beneficial in humans (...apart from when someone horrid doesn't wash their hands after wiping their bum before making you a lovely home made pie).

Seriously E. coli gets a bad wrap ....there are lots of different strains but generally you can happily have it in your gut with no bad effects. Probably best to quote the strain rather than just say E. coli since most E. coli strains are a good thing in your gut.

 

[M Paine]

If that's all their theory involves why use a ME/CFS population and why did you (and I) crowd-fund it?

If it's true that LPS and other microbial products are getting into the bloodstream and causing inflammation, that's an avenue for treatment.

 

[Marco]

If it's true that LPS is getting into the bloodstream and causing inflammation, that's an avenue for treatment.

But their own results suggest there's no evidence of elevated cytokines.

 

[adreno]

But their own results suggest there's no evidence of elevated cytokines.

Could it perhaps lead to autoantibody production instead?

 

[adreno]

Besides celiac disease, several other autoimmune diseases, including type 1 diabetes [13, 14], multiple sclerosis [15, 16], and rheumatoid arthritis [17], are characterized by increased intestinal permeability secondary to noncompetent TJs that allow the passage of antigens from the intestinal flora, challenging the immune system to produce an immune response that can target any organ or tissue in genetically predisposed individuals [18–21].

https://www.researchgate.net/profil...e_Diseases/links/0046352cae0af3b5df000000.pdf

 

[ljimbo423]

I thought immune system dysfunction in cfs was well established? If so, I don't understand why there are having such a hard time finding consistent levels of high or low cytokines.

Unless the cytokine profile is so different from person to person, they can't establish any consistency or patterns.

 

[justy]

The conclusions are comprehensive:

Source: https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y​

EDIT: got to the discussion section and here it is in their own words: "An altered microbiome is postulated to lead to increased gut permeability (“leaky gut”) and intestinal inflammation with gastrointestinal symptoms. Increased translocation of lipopolysaccharides (LPS) from gram-negative bacteria leads to autoantibody production, disruption of tight junctions, and both local gastrointestinal and systemic inflammation

Helen mentioned it, but I would like to reiterate that this is nothing new. KDM and others have been working on altered Gut microbiome and bacterial translocation in patients and in research.

best bet is to look at this as a very complex ecology that is out of balance rather than bugs we need to find and kill

I have bacterial translocation with a proven host of nasty gut bugs rampant in my blood stream. I'd quite like to be able to treat that directly.

If it's true that LPS and other microbial products are getting into the bloodstream and causing inflammation, that's an avenue for treatment.

Yes, I have this issue - high levels of inflammation, proven leaky gut and proven bacterial translocation. Ive done a long course of Rifaximin followed by probiotics, but I don't feel any better.

 

[arewenearlythereyet]

I have bacterial translocation with a proven host of nasty gut bugs rampant in my blood stream. I'd quite like to be able to treat that directly.

Hi @justy I don't have a big axe to grind here. My point is that we don't know what is really going on. Certainly treating with antibiotics as discussed earlier may do more harm than good. There is just not very much to say how common this is, how it works or how to treat it safely without potentially making things worse. It sounds reasonably plausible to me that when the immune system is compromised, that the body may be more susceptible to infection but this is just a theory, just like so many other theories around the so called "leaky gut" ....we just don't know enough to make any sensible attempts at a meaningful treatment without potentially making things a lot worse.

The issue really is to see why these "nasty bugs" are where they are....I doubt napalming them with antibiotics or whatever will do anything but give a temporary reprieve and could potentially do some damage. I see a lot of misconceptions when it comes to microbes and this is normally about oversimplification and treating it like some kind of "warfare" where the only desirable outcome is complete elimination.

Would you employ a gardener to weed your garden, whoose only tool to do it was a flame thrower? You might decide to enjoy your garden with the weeds if you knew the implications from the start.

It's a matter of weighing up the risks as with anything we have to deal with. I hope you didn't think that I was downplaying what you are having to go through.

 

[M Paine]

But their own results suggest there's no evidence of elevated cytokines.

My interpretation is that they did not find a common cytokine profile that distinguished patients from controls. "Elevated cytokines" is a bit of a misleading term, cytokines can be either more or less abundant, and pro or anti-inflammatory. What Mady Hornig and their team recognised, is that patients who have had this disease a short time, display a different cytokine profile than patients who have had the disease a long time. If you read the paper Distinct plasma immune signatures in ME/CFS are present early in the course of illness, you can see for yourself that when patient groups are split by duration of illness, the cytokine profiles are identifiable.

The authors of the paper we are discussing in this thread have made mention of this, and seem aware of the issue:

• No changes were observed in immune markers--a finding that may reflect the dearth of participants who had been ill for a short time; earlier research suggests immune changes may only be evident when comparing short and long duration cases

It might be that given a different cohort, the picture might be somewhat different. It's unclear. We know in other cases of long term immune activation, that the immune system has ways of dampening itself.

 

[TigerLilea]

It can also be quite beneficial in humans (...apart from when someone horrid doesn't wash their hands after wiping their bum before making you a lovely home made pie).

Seriously E. coli gets a bad wrap ....there are lots of different strains but generally you can happily have it in your gut with no bad effects. Probably best to quote the strain rather than just say E. coli since most E. coli strains are a good thing in your gut.

Mutaflor and Symbioflor 1 are both e-coli probiotics that have been shown to help some people with ME/CFS.

 

[M Paine]

Full paper here... https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y

I just noticed this was out of Ian Lipkins lab, which makes some of my previous comments about the authors seeming aware of Mady Hornig's work a little confused

 

[Forbin]

There may not be a "bad bug" that is directly altering the microbiome. The immune system's response to infection and injuries outside of the gut appears to be able inflict "collateral damage" on constituents of the microbiome. This might explain the multiple non-specific triggers of ME. Once the microbiome is out of balance, the immune system may come to directly regard some of the gut's constituents as a threat and act to suppress them. The immune system might then be suppressing the very bacteria that normally inhibit it from going after gut bacteria, creating a vicious cycle caused by the imbalance itself, not by any specific "bad actor" in the gut. Were this true, I wonder if B-cell depletion might break this cycle by giving the microbiome the "pause" necessary to return to a state that the immune system finds benign.

Just speculation, of course.

 

[Manganus]

Unless the cytokine profile is so different from person to person, they can't establish any consistency or patterns.

That would be my assumtion.

 

[alex3619]

Which makes me wonder even more - what's the point of this research?

Aside from we just do not know enough and need more evidence of what is going on, this research might give us a non-invasive biomarker for ME.

 

[alex3619]

If it's true that LPS and other microbial products are getting into the bloodstream and causing inflammation, that's an avenue for treatment.

I think some of the research mentions chemicals found in fruit and vegetables, especially apple skins, can help with LPS induced problems. I was going to blog on this some years back then my brain crashed again.

 

[alex3619]

But their own results suggest there's no evidence of elevated cytokines.

That is an observation, we need to be careful about interpreting it. Cytokine production might be impaired, or there might be other reasons.

 

[alex3619]

One way to think of the microbiome issue is as an ecology. This is not an ecology of just gut bacteria, but other microbes including viruses, and the human host as well. We still do not really understand how this works even in healthy people.