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

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
I suspect the quick cure will have strings attached... It will likely depend highly on the mix of issues that we have... For some of us, its going to be like killing a hydra:
a many-headed serpent or monster in Greek mythology that was slain by Hercules and each head of which when cut off was replaced by two others
As for viruses, I'm doubtful that many of them go away...after being on Valcyte for multiple herpes family viruses and IVIG for the past 10 months, I just had a flare of HSV2... it's pretty persistent...
 

LINE

Senior Member
Messages
832
Location
USA
I think that when the gut is imbalanced it's because of ongoing infection of some type and at some level, and the infection is not easily detected in the blood. Certain viruses and bacteria are notorious for leaving the blood stream and settling in various organs and even the brain. Hard to test for microbes in the brain.

I learned that testing is very hit or miss, in my case a protozoa parasite went undetected for some time which caused extreme sickness. There are many pathogens that can infect that are not studied or identified as pathogenic. I took a wide sweeping approach which is working.
 

ebethc

Senior Member
Messages
1,901
It shows that only 3 out of 10 ME/CFS patients had mild gut symptoms. So, 7 out of 10 ME/CFS patients reported no gastrointestinal symptoms at all. However they had a significant increase in intestinal permeability.

how was intestinal permeability tested?

What is also really interesting to me, is that the higher levels of bacterial sequences in the blood of the ME/CFS patients over controls, was maintained for 72 hours or 3 days.

This is the same time frame for the worst PEM symptoms for many people with ME/CFS.

this is completely plausible to me... subjectively, I feel like I have a low level sepsis, which is like a flu-ish feeling that ebbs and flows but is always there..
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
this is completely plausible to me... subjectively, I feel like I have a low level sepsis, which is like a flu-ish feeling that ebbs and flows but is always there..

That's a really good description of how I feel too!

how was intestinal permeability tested?

By the much higher levels of bacterial sequences (bacterial by- products) from the gut, found in the blood of ME/CFS patients over controls, after an exercise challenge test.

The higher levels of bacterial sequences in the blood show a clear indication of increased intestinal permeability (leaky gut) in the ME/CFS patients.

Jim
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
By the much higher levels of bacterial sequences (bacterial by- products) from the gut, found in the blood of ME/CFS patients over controls, after an exercise challenge test.

The higher levels of bacterial sequences in the blood show a clear indication of increased intestinal permeability (leaky gut) in the ME/CFS patients.
What test does the doctor order?
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
It looks like "16s ribosomal rna sequencing" is the method they used in the study. However, I don't know if it can be ordered by a doctor.
LINK

In another study, in which Susan Levine and Maureen Hanson were part of, they used sCD14, LBP (lipopolysaccharide binding protein) and LPS as measurements for microbial translocation.

Markers for microbial translocation, sCD14 and LBP, were measured in plasma samples by commercially available enzyme-linked immunosorbent assays (ELISA).

Plasma sCD14 was quantified using the Quantikine Human sCD14 Immunoassay (R&D Systems, Minneapolis, MN), and plasma LBP was measured by LBP soluble ELISA kit (Hycult Biotechnology, Uden, The Netherlands) according to the manufacturers’ protocols.

Plasma bacterial endotoxin, i.e., LPS, was measured from heparinized blood samples (Brandtzaeg) using the Limulus Amebocyte Lysate (LAL) assay (Lonza Group Ltd, Allendale, NJ).
LINK

I don't know if you can get the sCD14 and LBP tested through a doctor but the LPS test can be ordered through a doctor I think. My big concern about having a LPS test done without exercising though, is that it might not give a full and accurate picture of the translocation of LPS.

My guess is that's why the researchers are using exercise to analyze bacterial translocation.

Jim
 

bertiedog

Senior Member
Messages
1,738
Location
South East England, UK
Many years I did Dr DeMerlier's urine test for LPS and my reading showed the highest level. Not sure how legit the test is but interesting and I am positive I do have a leaky gut and SIBO plus Candida to complete the dysregulated picture.

No matter how hard I work on my gut though my immune system remains completely under functioning.

Pam
 

Dan_USAAZ

Senior Member
Messages
174
Location
Phoenix, AZ
how was intestinal permeability tested?

By the much higher levels of bacterial sequences (bacterial by- products) from the gut, found in the blood of ME/CFS patients over controls, after an exercise challenge test.

The higher levels of bacterial sequences in the blood show a clear indication of increased intestinal permeability (leaky gut) in the ME/CFS patients.

Several years ago I took a blood test for intestinal permeability that looked for levels of gut bacteria antibodies in the blood. If I remember correctly, they checked for 10 different bacterial antibodies and the result was a number for each type that they then rated as Low, High or Very High. The theory behind this test is that there should be little to none of these antibodies in the blood, because these gut bacteria should never translocate from the gut.

Does this sound like an appropriate approach or was I scammed?
 

unicorn7

Senior Member
Messages
180
Yes, that’s a good test. You can do a lot of tests and combine the results to get a clear picture.

I had cd14 tested, it’s a marker for LPS in your blood. Zonuline is a marker of leaky gut. Antibodies against gut bacteria in your blood is a marker as well.
They were all out of range with me.

I think IgG/IgA testing on food is also a measurement for leaky gut. When you have a lot of antibodies against food, that says something about how much contact there is between food particles and your immune system.
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
Several years ago I took a blood test for intestinal permeability that looked for levels of gut bacteria antibodies in the blood. If I remember correctly, they checked for 10 different bacterial antibodies and the result was a number for each type that they then rated as Low, High or Very High. The theory behind this test is that there should be little to none of these antibodies in the blood, because these gut bacteria should never translocate from the gut.

Does this sound like an appropriate approach or was I scammed?

Hi Dan_USAAZ - It sounds like the same kind of testing Micheal Maes did in this study.

He found high levels of antibodies to lipopolysaccharides (LPS) in the blood of CFS patients. Treated them for increased Intestinal permeability (leaky gut) and the LPS antibodies levels dropped as the patients gut healed.

So it seems to be a good test. The IgA and IgM mentioned below are the antibodies Maes tested to the LPS in the blood of patients. NAIOSs are "natural anti-inflammatory and anti-oxidative substances"

RESULTS:
Subchronic intake of those NAIOSs significantly attenuates the initially increased IgA and IgM responses to LPS of gram negative bacteria.

Up to 24 patients showed a significant clinical improvement or remission 10-14 months after intake of NAIOSs.

A good clinical response is significantly predicted by attenuated IgA and IgM responses to LPS, the younger age of the patients, and a shorter duration of illness (< 5 years).


DISCUSSION:
The results show that normalization of the IgA and IgM responses to translocated LPS may predict clinical outcome in CFS.

The results support the view that a weakened tight junction barrier with subsequent gut-derived inflammation is a novel pathway in CFS and that it is a new target for drug development in CFS.

Meanwhile, CFS patients with leaky gut can be treated with specific (NAIOSs) and a leaky gut diet.
LINK


Jim
 

M Paine

Senior Member
Messages
341
Location
Auckland, New Zealand
LPS should trigger certain toll like receptors, such as TLR4. IL12 should be increased as a result, and a quick pubmed search for cytokine studies of CFS patients brings up studies where they do see elevated IL12.

Can't say I feel confident about what causes translocation of microbial products like LPS, but I really hope to see more people researching this avenue. There's a lot of viable evidence for translocation.

I personally want to see if T cell clonal expansion targets LPS. I know Mark Davis is trying to find common binding sites for expanded T Cell populations from patients, LPS components would be such an easy thing to screen for I might have though.
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
Last edited:

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
So, again as dumb consumers, what test can WE or our doctors (not researchers) order to see if we have LPS??

If we can't test and see if we have the problem or not, its hard to solve a problem we may or may not have. It's hard enough dolving the problems we do have...

A series of tests accessible to patoents would be acceptable.

Then, if we do have LPS roaming around, translocating, etc. causing T cell clonal expansion, TLR or cytokine activation, what treatments does one apply to fix the problem???

...bearing in mind that many of us are already on high quality diets, taking ample prebiotics and high quality probiotics?

It's great to theorize about this, but some real life applicability would be nice...
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
So, again as dumb consumers, what test can WE or our doctors (not researchers) order to see if we have LPS??

I have read of many people here getting LPS and zonulin blood testing done but I haven't done it myself. So those tests are available.

@unicorn7 says she had a cd14 test done, it’s a marker for LPS in your blood. Zonulin is a marker for leaky gut.

Then, if we do have LPS roaming around, translocating, etc. causing T cell clonal expansion, TLR or cytokine activation, what treatments does one apply to fix the problem???

...bearing in mind that many of us are already on high quality diets, taking ample prebiotics and high quality probiotics?

The only other things that I'm doing is taking daily anti-microbial herbs like oil of oregano, holy basil, thyme, olive leaf extract etc. and numerous supplements to help heal my gut.

My view is that I have to get the bacteria re-balanced in my gut to bring down the inflammation, both in my gut and systemic inflammation, so my gut can heal.

It feels like that's what's happening, even though I can only tolerate fairly small amounts of anti-microbial herbs. I am definitely getting healthier!:)

Diet and prebiotics I don't think will be enough for most people with ME/CFS. Anti-microbial herbs and supplements to heal the gut will also be necessary.

Jim
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
I have read of many people here getting LPS and zonulin blood testing done but I haven't done it myself. So those tests are available.
Since you have been so kind to bring this to our attention, perhaps you could help by figuring out what tests they are.
@unicorn7 says she had a cd14 test done, it’s a marker for LPS in your blood. Zonulin is a marker for leaky gut.
So, looks like ARUP labs will do CD14.

Zonulin is one marker of leaky gut, so are multiplying food allergies, digestive issues, skin problems like eczema, and nutrient deficiencies.
The only other things that I'm doing is taking daily anti-microbial herbs like oil of oregano, holy basil, thyme, olive leaf extract etc. and numerous supplements to help heal my gut.

My view is that I have to get the bacteria re-balanced in my gut to bring down the inflammation, both in my gut and systemic inflammation, so my gut can heal.

It feels like that's what's happening, even though I can only tolerate fairly small amounts of anti-microbial herbs. I am definitely getting healthier!:)
Glad it's working for you. But, it is not the same for everyone.

Let's think about that statement - antimicrobial herbs. Which microbes are bring killed? These gut microbes work together in communities. Some support or complement each other. Some kill others off. Your interventions may just be the perfect thing for you but a disaster for someone else.
Diet and prebiotics I don't think will be enough for most people with ME/CFS. Anti-microbial herbs and supplements to heal the gut will also be necessary.
One must remove food allergens and foods with pesticides like RoundUp and toxins. And Candida, parasites, and viruses. One needs to restore the gut lining - glutamine and glycine can be helpful, while supporting phospholipids for cell membranes. Then supplying prebiotics and high quality probiotics.

It helps to know if you have bad actors in your gut and target interventions that kill things, like antimicrobial herbs ONLY if you have something thst needs killing.

However, it's not that easy. It can take many months of work to restore a microbiome. And no one knows what a perfect microbiome looks like. The science is not there.

And, even if one has a gut in good shape, one can still be sick. When I was at my sickest 2 years ago, sleeping 16 hours a day and unable to think straight and see straight, my dictir said i had one of the best looking stiol tests he'd ever seen. Now, however, whrn im doing much better, after 2 months of oral antibiotics, 4 months of IV antibiotics, and 3 months of 350 billion probiotics with herbal supplements and multiple high quality prebiotics, my gut has low diversity and the probiotics don't seem to be doing much. But im much more functional.

We are heterogeneous in this disease. The LPS theory is very interesting, but we need actionable information we can use.

If you find LPS with a CD14 test, then what?? What if you have bacterial translocation? Can you fix it? Fixing the gut is one issue, but this seems to be travelling into new territory. The info is not much use unless we can act on it and it changes our outcome...
 

Dan_USAAZ

Senior Member
Messages
174
Location
Phoenix, AZ
what - specifically - are NAIOS? do you have a list? thx

I found examples of NAIOSs (natural anti-inflammatory and anti-oxidative substances) in the Maes paper.

They list examples as
glutamine
N-acetyl cysteine
zinc​

I have taken all three of these with no perceived improvement to my post exercise gut issues. I actually had to quit taking glutamine a few years ago because it appeared to be making my gut issues much worse.

For context, in regard to my "post exercise gut issues", after resistance training I will experience gut pain, inflammation and diarrhea for anywhere from 6 to 36 hours. The duration is directly correlated to the intensity and duration of the exercise. The gut issues appear to drive extreme fatigue and cognitive dysfunction. The fatigue and cognative issues persist for some time after the gut has stabilized.

While I think these theories may have some validity for me, I am not sure the solution will be as simple as taking NAIOSs. I will be vary curious to see where this line of research goes.
 

ebethc

Senior Member
Messages
1,901
I found examples of NAIOSs (natural anti-inflammatory and anti-oxidative substances) in the Maes paper.

They list examples as
glutamine
N-acetyl cysteine
zinc​

I've had good luck w zinc; glutamine is just okay.. helps w brain fog a bit, but only sometimes..

I'm currently taking GOS (bimuno) + Align probiotics, and a little l plantarum, plus Neem... GOS feeds the Align so that it "sticks" in your gut vs passing right through... I don't believe that GOS directly "fixes" leaky gut, but it can reduce the endotoxins, which is helpful whilst addressing leaky gut in other ways... I just started it today, so nothing to report yet. Fix Your Gut has more info; here is one of the articles.. Also discussion on their forums


https://fixyourgut.com/recommended-prebiotic/
 

unicorn7

Senior Member
Messages
180
If you find LPS with a CD14 test, then what?? What if you have bacterial translocation? Can you fix it? Fixing the gut is one issue, but this seems to be travelling into new territory. The info is not much use unless we can act on it and it changes our outcome...

I agree with you that there is a lot of treatment options missing still.
It’s really hard to change your (leaky) gut and microbiome, even if you keep testing it and checking.

I think one of the problems is that because it is not “mainstream” yet, that we don’t treat it until you have had it for years. I think it gets harder and harder to treat the longer you have it.

Another problem is that I think this problem can only be treated by a personalized treatment plan and how do you test that in a protocol.

What helped for me is treating the dysbiosis (sibo) constantly, giving the immune system support for getting the LPS out (LDN, immunoglobulins), trying to influence the microbiome (probiotics), treating inflammation in the gut (curcumine, mesalazin, omega 3)
I don’t think any of those things would have worked on their own, so it wouldn’t do well in a study.