ME/CFS researcher Derya Unutmaz's hypothesis on cause of ME/CFS....

[AngelM]

The POTS and Orthostatic Intolerance diagnoses are confusing for me. A tilt table test was used as a diagnostic for CFS in the late nineties, and perhaps it still is. I only remember that the tilt table technicians had to stop my test after three minutes because the readings on the heart monitor became dangerously high of low, but after all these years not quite sure what was being monitored.

Interesting that your POTS is worse when you do housework, bending down, moving around. It is when I stand or sit still for more than a few minutes that my fatigue is exacerbated. Only in the last month, after reading about a POTS victim in a magazine article, did I begin to take OT seriously. Cooking has always been an issue for me. I dismissed my avoidance of cooking or baking as just “not being very good at it,” but now I believe the problem all along was that cooking involves standing in one place for more than a few minutes whether doing food prep, stirring a pot, or washing dishes. I remember being so exhausted by the time I sat down for a meal that I couldn’t eat. Over the long term, I feel bad for my children, for whom dinner time was never the “Leave it to Beaver” experience they deserved.

 

[Wishful]

@JES , exercise does more than alter the gut permeability. What you describe makes me think it's more likely that you're straining muscles in ways that you aren't used to, which damages some muscle cells, which in turn triggers the t-cells to clean up the debris, releasing cytokines which affect ME/CFS. I get PEM from non-standard physical activity. I can do hours of strenuous activity that I'm used to without triggering PEM, but a few minutes of straining muscles differently will trigger PEM. My delay is 24 hrs though, which is consistent with IFN-g production following muscle damage.

It may be that muscle damage from activity triggers immune system activation, which might then result in at least some of the increased gut permeability observed by the researchers. I didn't follow all the technical details of the report in the link, but it sounded like they were finding increased gut permeability in response to very high levels of physical activity, far beyond what I do. I can't see washing windows for a couple of minutes causing leaky gut syndrome, though that does trigger PEM for me. The exercise->leaky gut link might be a factor for a subgroup of ME/CFS, but I really don't feel that it's a factor for me. The timing and variability (lack of) just doesn't seem to fit. The muscle damage -> cytokine hypothesis does fit well.

 

[raghav]

@FMMM1 @perrier I see that you two are using Restore liquid. I bought a bottle of it (very costly) and started at 5ml thrice a day. I took it for 4 days within which time I developed knee pain, headache and tiredness. I have stopped it temporarily. How is your experience with it ? Did you get any side effects ?

 

[perrier]

@FMMM1 @perrier I see that you two are using Restore liquid. I bought a bottle of it (very costly) and started at 5ml thrice a day. I took it for 4 days within which time I developed knee pain, headache and tiredness. I have stopped it temporarily. How is your experience with it ? Did you get any side effects ?

Dear Raghav

Our family member is using it, no side effects, no benefits. Niente, as they say.

I seem to recall you did a FMT in Tampa. Any updates on that.

 

[raghav]

Thanks for replying @perrier You are mistaking me for somebody else. I have never been outside of India.

 

[FMMM1]

With everyone's interest in the microbiome, where isn't there any research into Fecal Microbiota Transplants (FMTs) in CFS/ME patients? I would think that would be the easiest and fastest way to reverse (even if temporary) the microbiome of CFS patients and best way to heal leaky gut.

There was one study in Australia by Dr. Bro in 2012 that did FMTs in CFS patients and he had 60% cure rate.

I'm surprised that this isn't talked about more.

I looked briefly at the DVD of Maureen Hanson's presentation at the 2018 Invest in ME Conference. She's working with a Norwegian Group on faecal transplants. Check the web for something on this.

 

[mariovitali]

I looked briefly at the DVD of Maureen Hanson's presentation at the 2018 Invest in ME Conference. She's working with a Norwegian Group on faecal transplants. Check the web for something on this.

I hypothesise that for most of ME/CFS patients, FMT will fail in the long run. The key regulator here are Bile Acids that ultimately bring Gut Eubiosis and it is these that we must sort out (=too much of them, too little of them, noit in ideal proportions)

Thank you for mentioning that, i will contact Professor Hanson with some new findings which i hope she will find useful.

 

[FMMM1]

I hypothesise that for most of ME/CFS patients, FMT will fail in the long run. The key regulator here are Bile Acids that ultimately bring Gut Eubiosis and it is these that we must sort out (=too much of them, too little of them, noit in ideal proportions)

Thank you for mentioning that, i will contact Professor Hanson with some new findings which i hope she will find useful.

If you can get access to the Invest in ME Research International ME Conference 2018 (DVD's) then you may be interested in Ron Davis's presentation. He mentions the metabolic trap research and the fact that the should be in a position to report on this "by the end of the summer" (or whatever wording). I assume this is linked to Bile Acids.

 

[mariovitali]

@FMMM1

Are there any mentions about Bile Acids Metabolism when Ron Davis is discussing the Metabolic Trap or this is your speculation?

I highly doubt that the Metabolic trap hypothesis involves Bile acids to be honest, of course i may be wrong.

 

[FMMM1]

@FMMM1

Are there any mentions about Bile Acids Metabolism when Ron Davis is discussing the Metabolic Trap or this is your speculation?

I highly doubt that the Metabolic trap hypothesis involves Bile acids to be honest, of course i may be wrong.

Ron Davis doesn't mention bile acids in his talk. However, we don't have the specifics of the metabolic trap; hopefully, we should know more in a few months.

 

[dannybex]

That makes a lot of sense to me, especially in the light of these 2 papers-

A review of published studies has found that people who exercise excessively may be prone to acute or chronic gut issues-

Investigators found that with increasing intensity and duration of exercise, there was a proportional increased risk of gut damage and impaired gut function.

Specifically, the cells of the intestine are injured and the gut becomes more leaky, allowing pathogenic endotoxins normally present and isolated to the intestine to pass into the bloodstream.

This scenario of 'exercise-induced gastrointestinal syndrome' may lead to acute or chronic health complications.

When I found this study and other similar ones awhile back it struck me that this might explain why marathoners and other high-level athletes come down w/ME/CFS. That, and the inner pressure (stress) they put on themselves to 'be the best'.

 

[ljimbo423]

When I found this study and other similar ones awhile back it struck me that this might explain why marathoners and other high-level athletes come down w/ME/CFS. That, and the inner pressure (stress) they put on themselves to 'be the best'.

I agree. From the research I've done, (which is more than I would like to admit!), intensive exercise increases intestinal permeability, which increases bacterial or bacterial toxin translocation from the gut into the bloodstream.

Once in the bloodstream these toxins trigger an immune response and systemic inflammation. The systemic inflammation, in turn, creates a more leaky gut or increases intestinal permeability, causing to some degree a locked, self-feeding cycle.


Systemic inflammation increases intestinal permeability during experimental human endotoxemia.

Systemic inflammation results in an increased intestinal permeability. The increase in intestinal permeability is most likely caused by inflammation-induced paracellular permeability, rather than ischemia-mediated enterocyte damage.

 

[perrier]

@FMMM1

Are there any mentions about Bile Acids Metabolism when Ron Davis is discussing the Metabolic Trap or this is your speculation?

I highly doubt that the Metabolic trap hypothesis involves Bile acids to be honest, of course i may be wrong.

Have your tried to contact Lipkin with your work and thesis? Cort just published a review of Lipkin's work, and he might take an interest in what you have.

 

[mariovitali]

Have your tried to contact Lipkin with your work and thesis? Cort just published a review of Lipkin's work, and he might take an interest in what you have.

Yes i plan to contact him in the next couple of days.

 

[Stretched]

Over the long term, I feel bad for my children, for whom dinner time was never the “Leave it to Beaver” experience they deserved.

I watched that show as a kid... . Aren’t most families too dysfunctional to parallel that fictional family-& ?

 

[MonkeyMan]

I agree. From the research I've done, (which is more than I would like to admit!), intensive exercise increases intestinal permeability, which increases bacterial or bacterial toxin translocation from the gut into the bloodstream.

Do other types of stress increase it too? For example, poor sleep?

 

[ljimbo423]

Do other types of stress increase it too? For example, poor sleep?

Yes, both physical and psychological stress can cause an increase intestinal permeability (leaky gut) to varying degrees, depending on the intensity of the stress.

 

[perrier]

Yes, both physical and psychological stress can cause an increase intestinal permeability (leaky gut) to varying degrees, depending on the intensity of the stress.

And the most dramatic question is:how in the heck can this be healed? the leaky gut??

 

[Wally]

* https://oap-journals.org/jnrt/article/592 - “Murky Water: Cyanobacteria, BMAA and ALS”

I don’t know if this article has been shared elsewhere on the Forum or in this thread, so I apologize if I am repeating a discussion that has occurred elsewhere. Tried to do a “search” to see if this paper came up and I did not find any links. So, I thought I would drop it in here and in a new Cyanobacteria thread I just posted (General Discussion/Other Health and News Subforum) should it be of interest to others to read.

*Note that this paper is discussing ALS, but the references to dysbiosis may be relevant to the discussion going on in this thread. For example -

Recent animal findings suggest that environmental factors maybe more important than genetic suseptibility in determining who manifests ALS. In animal models, the “non-pathogenic” composition gut microbiome dramatically determines colonic permeability even in genetically identical immunocompetent animals 16,17. Furthermore, emerging evidence has implicated key changes in the intestinal homeostasis that may be playing a role in the pathogenesis of ALS. On a structural level, scientists have discovered damaged tight junctions and reduced expressions of tight junction protein ZO-1 and the adherens junction protein, E-cadherin, in the intestines of an ALS mouse mode 18. These mice, who express mutant superoxide dismutase (SOD1), also demonstrated an increased number of abnormal Paneth cells, which specialize in secrete antimicrobial peptides including defensin 5 alpha. Of note were increased levels of IL-17, an inflammatory cytokine implicated in inflammatory bowel diseases. One can see how these changes could significantly alter the intestinal integrity and affect the microbiome of the gut. In fact, comparisons of the intestinal microbiomes of ALS patients with those of healthy patients showed significant differences in the ratios of bacteria in multiple genus, including a reduction of beneficial microorganisms Oscillibacter, Anaerostipes, and Lachnospiraceae19. Conversely, harmful microorganisms including Dorea were found to be increased in ALS patients. Put together, these new findings provide further evidence of a link between the gut and the pathogenesis of the disease.

The possible tie in to the hypothesis that cyanobacteria may relate to M.E. outbreaks is explained in a couple of threads here on the Forum. @Hip does a good job of laying out this hypothesis in the post linked below. See, Hip’s Reply No. 114 on page six (6) at https://forums.phoenixrising.me/ind...ntolerance-is-not-me.51792/page-6#post-856637.

Perhaps this information might be useful to researchers who were not aware of the environmental factors occurring in these locations at the same time that reported M.E./C.F.S. cluster outbreaks took place.

 

[mariovitali]

Yes i plan to contact him in the next couple of days.

cc : @perrier

I just contacted Professor Lipkin. I attached Fibroscans and references on how Gut Microbiome dysbiosis may be responsible to Liver Pathology (and vice versa).


I will send today similar emails to Derya Unumtaz and Maureen Hanson. My goal is to convince them to shift some of their attention to the Liver and to the fact that impaired Bile acid metabolism can be responsible for Gut Dysbiosis in many cases. This essentially means that FMT will ultimately fail in a number of patients since impaired Bile acid metabolism will lead again to Gut Dysbiosis.

Gut and Liver work together, this is a fact.