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

[Moof]

This is the thing, it's not clear what "leaky gut" is caused by...My point is, I wouldn't waste my time and effort on any leaky gut routine.

Same here. Leaky gut is often but not inevitably associated with ME (I've only been symptomatic for the last 12 years, but I've had ME since the mid-1970s), and it certainly isn't unique to ME. It's so widespread, and there are so many confounding factors for those trying to study it, that it could be a long while before it's fully understood.

I know I have a couple of severe food intolerances, and they're all I focus on nowadays – nothing else has ever really made a difference. It doesn't get any worse during ME relapses or remit during better phases, it just seems to be a condition that runs in parallel. Other women in my family also developed it after menopause, so I think it may just be another one of the joys of ageing for us!

 

[ljimbo423]

On May 24, 2018, Anthony L. Komaroff, MD, Simcox-Clifford-Higby Professor of Medicine at Harvard Medical School and Senior Physician at Brigham and Women’s Hospital, presented on “Hot Areas in ME/CFS Research.” With increased momentum in research over the past two years, this SMCI webinar was a timely update to his popular presentation from SMCI’s 2016 webinar series that addressed current understanding of the role of various systems – including the brain, energy metabolism, genes, and immune system – in the pathophysiology of ME/CFS.

The webinar audience submitted many compelling questions – more than we had time for during the Q&A period. To follow-up with the community, Dr. Komaroff addresses some additional questions submitted during the webinar below. To access a full recording of the presentation, click here.


Q: You reported that in people with ME/CFS there are both increased immune activation and abnormalities of microbiome abnormalities (with associated “leaky gut”). Does the first cause the second, or does the second cause the first?

Komaroff: We don’t know. Either possibility is plausible, and it may be one way in some patients, and the other way in other patients. Nevertheless, if I had to guess, I’d bet that a primary abnormality of the microbiome was most likely.

And any discussion of infectious causes of ME/CFS must now consider the possibility that the microbiome—the collective genes of the various microorganisms that live on us and within us—may be a cause of ME/CFS.

link

Jim

 

[FMMM1]

link

Jim

I'm guessing that this would be consistent with the metabolic theory (trap etc). I.e. altered microbiome (which is caused by the altered metabolism) causes the fatigue i.e. primary symptom in ME/CFS.

I came across some stuff on the web which highlighted that many diseases, associated with ageing, may be a result of leaky gut; the leaky gut may be related to altered metabolism of melatonin/tryptophan. E.g. if you google some thing like "melatonin tryptophan leaky gut" you come up with a bunch of stuff regarding altered microbiome as the origin of disease (Parkinsons disease - https://www.ncbi.nlm.nih.gov/pubmed/27604608).

This is complicated stuff. On the plus side if others are interested in leaky gut/origin of -- then this may be of assistance to us. Also, thankfully we seem to be getting some good researchers interested e.g. OMF; hopefully, they can get funding/we can help lobby for same. E.g. anyone think of a way to put pressure on the Europeans (MEPs etc) to fund research into ME/CFS via Horizon 2020 [€/$80 billion budget]?

 

[FMMM1]

It was actually a measurement of my intestinal tract PH not my stomach. Mine was measured by a stool sample.



Yes. The PH in my gut (intestines) was 7.9. The reference range was 6.0-7.2. So the PH of my GI tract is a great breeding ground for pathogenic bacteria.

You may wish to contact Chris Armstrong (Melbourne University/OMF) he was interested in measuring gut pH. He may be interested in your data.

 

[bertiedog]

It was actually a measurement of my intestinal tract PH not my stomach. Mine was measured by a stool sample.

Yes. The PH in my gut (intestines) was 7.9. The reference range was 6.0-7.2. So the PH of my GI tract is a great breeding ground for pathogenic bacteria.

Mine was similar and I definitely have low stomach acid, lots of pathogenic bacteria plus Candida and low gut diversity. Yet I take HCL with my meals and a good digestive enzyme plus targeted probiotics and around 35g of fibre daily. However my microbiome refuses to improve! Something is holding it back. I also have a very weak immune system and readily pick up viruses which sometimes go into an infection.

Pam

 

[ljimbo423]

Mine was similar and I definitely have low stomach acid, lots of pathogenic bacteria plus Candida and low gut diversity. Yet I take HCL with my meals and a good digestive enzyme plus targeted probiotics and around 35g of fibre daily. However my microbiome refuses to improve! Something is holding it back. I also have a very weak immune system and readily pick up viruses which sometimes go into an infection.

Pam

I hear you Pam. I feel very frustrated that changing my gut health is going much slower than I would like it to. I think there could be a few reasons for that.

You mentioned having a weak immune system. That could allow the pathogenic bacteria to overgrow in your gut.

Low grade inflammation in ME/CFS is what some the ongoing research is focused on.

I think that low grade systemic inflammation, could be and probably is making it much harder to heal increased intestinal permeability (leaky gut).

Inflammation causes an increase in intestinal permeability and intestinal permeability causes increased inflammation from toxins entering the bloodstream.

There are also biofilms that pathogenic bacteria in the gut form, that protect them from antibiotics and antibiotic herbs. These biofilms can be very difficult to penetrate to get at the bacteria that hide in them.

I have just started becoming more and more aggressive in treating dysbiosis and leaky gut. Increasing my doses of antibiotic herbs and I think next I will find some strong biofilm "breakers" to get at the very stubborn bugs!

Jim

 

[FMMM1]

Mine was similar and I definitely have low stomach acid, lots of pathogenic bacteria plus Candida and low gut diversity. Yet I take HCL with my meals and a good digestive enzyme plus targeted probiotics and around 35g of fibre daily. However my microbiome refuses to improve! Something is holding it back. I also have a very weak immune system and readily pick up viruses which sometimes go into an infection.

Pam

Interesting.

 

[junkcrap50]

I wonder what fixes "leaky"???

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.

 

[perrier]

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.

Hello
Yes, Dr Borody did a small study. And I have wondered too why FMT hasn’t been looked at more. There are a few folks here who did it, perhaps their posts can be reviewed.

 

[junkcrap50]

Hello
Yes, Dr Borody did a small study. And I have wondered too why FMT hasn’t been looked at more. There are a few folks here who did it, perhaps their posts can be reviewed.

I've done a course (14) of at home FMTs, but never wrote about them in depth here. I noticed definite and immediate improvement. But, it lost all improvements shortly after, because I changed my diet and took lots of fiber (soluble and insoluble) and lots of prebiotics (did the potato startch thing), which I'm convinced harmed the FMTs.

 

[MonkeyMan]

I did FMT. It helped my BM's, but didn't make a difference to the ME/CFS

 

[Wishful]

There we go: drewmaster disproves the 'dysbiosis causes ME/CFS' hypothesis!

Okay, real-life evidence against it anyway.

 

[ljimbo423]

There we go: drewmaster disproves the 'dysbiosis causes ME/CFS' hypothesis!

Okay, real-life evidence against it anyway.

Here's some evidence for dysbiosis as a cause in ME/CFS as Ian Lipkin, Derya Unutzman and Chris Armstrong are saying-

This is a quote from Thomas Borody's study on Fecal microbiota Transplantation (FMT) in ME/CFS-

Results: 35/60 patients who underwent initial bacteriotherapy responded to treatment. 10/15 patients who failed this course were offered a secondary transcolonoscopic infusion followed by a rectal infusion or an oral course of cultured bacteria.

Of these 7/10 responded, giving a total of 42/60 (70%) patients who responded to treatment. Contact was achieved with 12 patients after 15-20 year follow-up.

Complete resolution of symptoms was maintained in seven of the twelve patients and 5/12 did not experience recurrence for approximately 1.5-3 years post bacteriotherapy.

Conclusion: Bacteriotherapy achieves initial success rate of 70% in CFS and a 58% sustained response.

Given that manipulation of the colonic microbiota improved CFS symptoms, bacteriotherapy for CFS warrants further investigation and may provide further insight into a possible etiology of CFS.

LINK

Jim

 

[M Paine]

There are a lot of anocdorsl reports of fecal transplant leading to temporary relapse. It seems like repopulating the microbiome isnt enough, like there is some other process occurring which leads to dysbiosis.

Same goes for antibiotic use. People report brief relapse after antibiotic use.

There's almost no doubt that dysbiosis and leaky gut are causing or correlating to the signs of disease. The thing which you have to ask, is if dysbiosis is the root cause, why is FMT not curative. The answer may be that dysbiosis is not the root cause of illness, but instead a cause of the symptoms of the illness.

 

[ljimbo423]

There are a lot of anocdorsl reports of fecal transplant leading to temporary relapse. It seems like repopulating the microbiome isnt enough, like there is some other process occurring which leads to dysbiosis.

Same goes for antibiotic use. People report brief relapse after antibiotic use.

The same thing happens in people without ME/CFS that have SIBO/dysbiosis. If you follow or listen to functional medicine doctors, that have been treating SIBO and dysbiosis for years.

They say that treating dysbiosis is often extremely difficult and relapses are not the exception but the norm. Treatment often includes the use of antibiotics or a combination of herbs and antibiotics, with diet etc, and relapse is still very, very common.

It seems to me the relapse from SIBO/dysbiosis treatment is not limited to ME/CFS but is the norm.

Jim

 

[AngelM]

Unetmaz’s hypothesis seems closer to the mark than any research I’ve studied thus far. Perhaps because it relates directly to my experience over the past 35 years.

Using the desert island question as a model, if I were stranded on a desert island with a CFS researcher and allowed only three comments about what seems most significant to me anout my experience with this illness, I would say: one—that my illness began after a serious viral infection, in my case mononucleosis; two— though it made no sense to me (or gastro specialists) at the time, severe stomach/lower abdominal pain ALWAYS preceded and accompanied months of profound and debilitating fatigue; and three—on the day begore my worst and most severe crash, I was in training for a 6K race, had pushed myself to the absolute limit of my physical ability, and felt very well; however, less than 24 hours later, I lacked the physical strength to get out of bed or function at any level of normalcy—and have not had a significant period of remission since.

I’m curious about what others might say if they found themselves on this same desert island. I would think such condensed reports would be helpful to CFS researchers.

 

[ljimbo423]

on the day begore my worst and most severe crash, I was in training for a 6K race, had pushed myself to the absolute limit of my physical ability, and felt very well; however, less than 24 hours later, I lacked the physical strength to get out of bed or function at any level of normalcy—and have not had a significant period of remission since.

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

Paper #1-

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.

LINK

Noncommunicable diseases (NCDs), also known as chronic diseases, tend to be of long duration and are the result of a combination of genetic, physiological, environmental and behaviors factors.

LINK

Paper #2
Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability-

Chronic non-communicable diseases (NCDs) are the leading causes of work absence, disability, and mortality worldwide.

Most of these diseases are associated with low-grade inflammation. Here, we hypothesize that stresses (defined as homeostatic disturbances) can induce low-grade inflammation by increasing the availability of water, sodium, and energy-rich substances to meet the increased metabolic demand induced by the stressor.

One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system.

Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation.

In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state.

We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases.

LINK

 

[ljimbo423]

my illness began after a serious viral infection, in my case mononucleosis;

This paper could help explain how Mononucleosis triggered your illness. The systemic inflammation from the Mononucleosis could have increased your intestinal permeability, triggering your illness-

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.

LINK

 

[AngelM]

Wow, this information is amazing. I had heard of pieces of it, like leaky gut, but was never quite able to put it into the CFS puzzle. I certainly had never connected my stomach issues with over-exertion, something I have done all my life. If the person on the treadmill beside me was running faster, I always turned up the speed and raised the elevation on my treadmill. Crazy, I know. I guess it falls under the category of “competitive?” Or “compulsive? Though I never really thought of myself in that way. Perfectionist, YES! Thank you a hundred times over!

 

[JES]

Regarding leaky gut, I've also had a few interesting revelations. I don't get PEM and never had a classic PEM response to exercise, but I recently developed pretty bad POTS. Few weeks ago I made the connection that my POTS symptoms and blood flow worsens significantly after certain type of exercise. Like for example cleaning the house or doing something where I have to move a lot up and down and stretch my body. The worsening comes with a two or three hours delay after the activity. Whereas if I go for a walk, even a longer one, I don't get any specific increase in POTS other than baseline symptoms. I probably had this for a long time, but never made the connection that the type of activity would matter.