Article A Gut-Immune-Energy Model: Pt. II – The Armin Alaedini Interview

[Cort]

This is the first Health Rising post to appear on PR. Fittingly, it's by Bronc - a PR member.

Health Rising covered this fascinating gut/immune/metabolic study in an earlier blog. Now Bronc is back with an interview with Dr. Armin Alaedini – the senior author of this study. Note that we just covered a study suggesting that the gut could play a major role in the low serotonin levels, ACE2 dysregulation, and at least some of the autonomic nervous system and immune issues in ME/CFS.


First, Bronc, a patient in the UK, gives us a brief update on the situation with the health service there and then dives into the Alaedini interview.

Update From the UK​

Here in the UK, the Department of Health and Social Care has announced a plan to improve the care provided to people with ME. It includes an acknowledgment that there has been a lack of biomedical research into ME but fails to acknowledge the very negative impact this has had on the lives of people living with the illness. It also fails to point the finger at those responsible for this – the National Institute of Clinical Excellence, and the Medical Research Council amongst others. It’s also one thing to call for more research into ME – as has been done – it’s quite another to provide the substantial sums of funding needed to accomplish that – and that has not happened.

At the same time, the DHSC has issued a consultation asking for views about the plan which includes a section about disability benefits and how the Department of Work and Pensions can improve the service it provides to those people who claim disability benefits. This tragically laughable comment ignores the war the DWP has waged on people claiming disability benefits since 2010. The DWP has consistently failed to acknowledge the debilitating nature of ME and instead focuses on the fluctuating nature of the illness to deny many people with ME disability benefits such as ESA and PIP. To compound matters, the British government recently announced that it wants to make it harder for people to claim disability benefits.

Thankfully, there is plenty of evidence revealing how people with ME suffer from a suppressed immune response, which accounts for many of the debilitating symptoms of the illness.

Suppressed Immune Response Could Account for Many of the Debilitating Symptoms of ME – An Interview with Armin Alaedini​

Dr. Alaedini has published 4 studies on gut issues in ME/CFS.
I recently talked with Dr. Armin Alaedini about his recent research into this issue. Dr Alaedini is an assistant professor at Columbia University and principal investigator at the Alaedini Lab. Its research is aimed at identifying ‘novel’ biomarkers, understanding disease mechanisms, and finding therapeutic targets in gastrointestinal and neuropsychiatric diseases.

He is also the chair of the ME/CFS Biospecimen Resource Access Committee at the National Institute of Neurological Disorders and Stroke and a member of the Neurobiology of Pain Study Section at NIH. He’s the senior author of 4 ME/CFS gut studies.

Dr Alaedini took time out of his busy schedule to talk to Bronc from Phoenix Rising about his research into ME, but first, check out what Suzanne Vernon – a co-author of the study – wrote on the Bateman Horne Center website about how the study happened. The genesis of this study, which dates back to 2009 – and the formation of the Solve ME/CFS Biobank – demonstrates why the Biobank and efforts like DecodeME can be so helpful.

Suzanne Vernon on the Genesis of This Study​

Intrigued by Alaedini’s work on post-Lyme Disease, in 2009, Suzanne Vernon – one of the study co-authors – asked him to collaborate on an ME/CFS study. Alaedini used some of the samples from that study for the 2023 study.

I met Armin Alaedini in 2008 at a meeting in San Francisco that was about solutions for Lyme and other tick-borne diseases through cutting-edge science. I was fascinated by his presentation on immunological findings in post-treatment Lyme disease and I approached him about collaborating on ME/CFS.

At this time, I had just started as the scientific director at the CFIDS Association, now Solve, and had the idea to set up a biobank of ME/CFS samples as a resource to drive and advance cutting-edge ME/CFS science. One year later, the biobank was jumpstarted because Science magazine published the paper describing an infectious retrovirus in the blood of ME/CFS patients.

Within days of that paper being published, blood banks and pharmaceutical companies were in search of blood samples from ME/CFS patients in order to validate the findings, develop tests and treatments. This motivated a collaboration between Solve and 5 ME/CFS clinical centers to collect blood samples from their well-characterized patient populations for biobanking and distribution to blood banks and pharma. Since that time, those precious blood samples have been used in multiple research studies (including this one).

In one of our first collaborations, Dr. Alaedini and his team at Columbia examined ME/CFS blood samples for signs of inflammation. Not finding evidence of inflammatory markers in ME/CFS, he suspected a defect in specific acute-phase immune responses in ME/CFS or a lack of the instigating microbes at the time of the blood draw.

To test this, he tapped into two different studies that had blood samples. The first were those 2009 blood samples from the SolveCFS BioBank that included 131 ME/CFS samples and 86 healthy control samples. The second were blood samples from a study led by Sanjay Shukla and Dane Cook. This super cool study (“Suppresssed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome“)used an exercise challenge to show that there was an increase in bacterial translocation into the blood and slower clearance from the blood following exercise in ME/CFS patients.

The result of this impressive collaborative research study is a compelling explanation for what could be causing PEM.

Check out the earlier study that this one built on.

The Armin Alaedini Interview​

• Antigen – any foreign substance that evokes an immune response in the body. Dietary antigen – a food particle that sparks an immune response; bacterial antigen – a bacterial particle that does the same. It’s usually the immune response that does the damage.
• Increased gut permeability – leaky gut; where the barrier between the gut and body breaks down – releasing bacteria and food particles into the bloodstream – causing an immune response.
• Bacterial and dietary translocation – the movement of gut bacteria and food particles through the gut wall into the bloodstream.
• Innate immune responses – the quickest immune response to damage or pathogen entry. Often associated with inflammation.

How did you get involved in the field of ME research?

I have always been interested in the study of complex medical conditions, especially those that are poorly understood and understudied. I became specifically involved in ME research because of my acquaintance with Dr. Suzanne Vernon, who at that time was the chief scientific officer at The Solve ME/CFS Initiative. I was fortunate to have her support for an NIH-funded project, which resulted in our recent publication that demonstrates how microbial translocation links gastrointestinal, immunologic, and metabolic defects in ME/CFS.

2) In the paper you co-authored, “Suppresssed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome“, it notes that the relationship between immunologic, metabolic, and gastrointestinal abnormalities remains unclear.

In your study, you examined two groups of people with ME: one at rest and one undergoing an exercise challenge. They were compared to a group of healthy people. Can you explain what differences you noted between the healthy control group and the people with ME and between the two groups of people with ME? What may have caused this elevated antibody response to microbial agents in people with ME?

I had been particularly intrigued by the fact that gastrointestinal complaints are common in ME/CFS. Data from the patients in our study clearly confirmed this, showing that gastrointestinal symptoms were indeed much more common and more severe in ME/CFS study participants than in the non-ME/CFS controls.

Along with this, we found a specific marker of injury or damage to the intestinal lining, called FABP2, to be higher in the blood of ME/CFS participants than in controls, providing a potential biological link to at least some of the associated gastrointestinal symptoms. Increased intestinal permeability due to damage can lead to greater translocation of dietary and microbial antigens, which are typically constrained within the gut lumen, across the intestinal barrier. This, in turn, may result in an immune response to those translocated dietary and microbial products to counter and remove the potentially inflammatory antigens from systemic circulation.

Indeed, our data pointed to a significant increase in antibody responses to microbial and dietary antigens in ME/CFS patients in comparison to controls. What especially surprised us, however, was the fact that we did not observe an expected rise in the more immediate, or what we call “acute-phase”, innate immune responses. Specifically, we found that despite the increased markers of intestinal damage and higher antibody responses, ME/CFS patients did not exhibit a significant acute-phase immune response to counter-circulating microbial products.

This was suggestive of a suppressed systemic immune response that could possibly explain some of the ME/CFS symptoms.

3) Your study also noted you found an ‘enhanced antibody response to dietary antigens in ME/CFS’. What might be causing this?

The antibody response to dietary antigens is likely part of the same process resulting from a dysfunctional intestinal barrier that results in an enhanced immune response to the contents of the gut lumen. These would include both microbial and dietary antigens that the immune system is generally tolerant to and does not mount a significant antibody response against under normal conditions.

4) People with ME suffer from post-exertional malaise which means that exercise will exacerbate their symptoms. What differences did you note between the healthy participants and people with ME who took the exercise challenge? What might be causing the differences in their response to exercise?

Intense exercise is known to cause increased intestinal permeability. Therefore, a maximal exercise challenge can be a particularly useful tool to better understand the effect of gut barrier function on the dysfunctional immune responses we were seeing in the ME/CFS cohort.

The data from the exercise challenge confirmed our earlier data, suggesting that ME/CFS patients have a dysfunctional immune response, characterized by a suppressed innate/acute-phase response that is ineffective at countering microbial translocation from the intestinal tract into systemic circulation.


At the same time, another part of the immune response, the adaptive immune system, tries to compensate for this dysfunction by producing antibodies against those microbial antigens. However, the antibody response appears to be inadequate, as the ME/CFS patients continued to have increased circulating microbial antigens. We hypothesize that these microbial antigens can trigger downstream inflammatory responses that impact the central nervous system and may contribute to some of the hallmark symptoms of ME/CFS, such as fatigue.

We also compared metabolic responses in response to exercise between ME/CFS and control study participants. Of particular significance, we found a suppression of glucose and citrate metabolic responses in ME/CFS that to some extent correlated with the suppressed innate immune responses in these patients. This dysfunctional metabolic response is not only conceivably capable of contributing to the observed immunosuppression in ME/CFS, but it may also further underlie energy deficits that drive ME/CFS symptomology.

Our data pointed to defects in specific metabolic responses involved in energy production, as well as in specific acute-phase innate immune responses that are supposed to counter microbial translocation by removing circulating LPS and other microbial components from blood.

But more interestingly, the suppression of these responses (metabolic and immunologic) correlated, suggesting a relationship or interaction between them that gives potential clues regarding causality. There is, in fact, prior data showing that suppressed glucose and citrate metabolic responses have a direct negative impact on innate immune responses.

Interestingly, those same metabolic responses in our study participants also correlated negatively with IL-10, an immunoregulatory cytokine that is known to be expressed in response to microbial products through different signaling pathways and to be particularly important as a key mediator of intestinal immune homeostasis.

We believe that the observed increase in IL-10 levels in ME/CFS during exercise limits the inflammatory reaction triggered by circulating microbial products, while enhancing the antibody-mediated clearance of translocated microbial and dietary antigens, as was clearly seen in our study.

There is also data from previous studies indicating that glucose deprivation can upregulate IL-10 production. So, there seems to be a mechanism here whereby the suppression of metabolic responses involved in energy production not only directly dampens the innate immune cell function, but it also enhances IL-10 production, which further limits the expression of acute-phase immune responses that are meant to counteract microbial translocation.

There is data from other studies indicating that uncontrolled microbial translocation is associated with neuroinflammation and cognitive dysfunction in the context of other conditions. This is important, because brain imaging studies in ME/CFS are in fact suggestive of low-level neuroinflammation and altered brain function in conjunction with impaired cognitive performance and other associated symptoms, including in response to exercise.


5) In your study, you observed an increase in antibody responses to both microbial and dietary antigens, reflecting greater epithelial cell damage, which point to enhanced translocation (movement) of gut luminal antigens across a compromised intestinal barrier in ME/CFS. Did your findings point to a possible treatment for this damage to the intestinal barrier?

Indeed, the data point to a number of potential targets to consider for therapy in the context of ME/CFS. These include reducing or repairing the intestinal damage in order to decrease the microbial translocation; blocking or sequestering the already translocated microbial antigens; reversing the identified defects in the acute-phase immune responses towards the microbial antigens, and targeting the suppressed metabolic pathways.

Indeed, it may include medications directed at the targets I previously mentioned, such as specific immunomodulatory agents, or inhibitors of intestinal barrier dysfunction, or activators that reverse the observed metabolic dysfunction.

As we don’t yet fully understand the cause-and-effect relationship between these potential immune, gut, and metabolic targets, more research is needed to better characterize the interaction between them in order to move this research toward the development of effective therapies.

Dietary approaches can certainly be envisioned to have a role in treatment because diet can impact the specific pathways involved. For example, dietary change alters the gut microbial population, which can lead to positive changes in gut barrier function, or it can lead to the production of certain metabolites by the gut bacteria that potentially counteract energy-producing metabolic dysfunction in the body.

6) What further research is needed to address the issues highlighted in your study?

More research is needed to better understand the relevance and level of contribution of the identified defects in the intestinal barrier, immune response, and metabolic pathways to ME/CFS symptomology, as well as to further characterize the molecular pathways involved, in order to move this research closer to development of effective treatments for ME/CFS.

The article suggested that endotoxemia (the presence of bacterial toxins in the blood) could be causing many symptoms in ME/CFS. If endotoxemia is present in ME/CFS, what would it take to show that?

We already have direct data pointing to low-grade endotoxemia in ME/CFS. In the recent study we published, we not only showed an increased immune response to microbial antigens but also increased levels of LPS in response to exercise in ME/CFS patients compared with healthy controls. Other groups have also shown increased microbial products, like bacterial DNA, in ME/CFS.

Taken together, the data point to low-grade endotoxemia that may explain many of the symptoms associated with ME/CFS, such as fatigue and flu-like symptoms.

The GIST​

• Thanks to Bronc from Phoenix RIsing for allowing Health Rising to post his interview with Dr. Armin Alaedini. Dr. Alaedini recently published a remarkable study suggesting that problems in the immune system, the gut, and the metabolism could be “conspiring” together to produce post-exertional malaise in ME/CFS
• Using samples stored in the Solve ME Biobank, some of which dated back to 2009 and the XMRV saga, this study took a deep dive into the immune system, the gut, and the metabolism.
• The results made it clear that exercise was indeed causing ME/CFS patients’ guts to leak – spilling gut bacteria and food contents into the blood. As that happened, one side of the immune system – the antibodies – leapt into action. Another side, though, the early inflammatory immune response did not.
• Plus an anti-inflammatory factor called IL-10 that knocks down the early immune response and interferes with glucose metabolism was elevated in ME/CFS – setting the stage for impaired energy production.
• This study found that while exercise significantly increased the levels of two key energy factors (citrate, glucose) that power the early immune response in the healthy controls, it did not do so in ME/CFS.
• That suggested that the early immune response against the bacterial invaders simply didn’t have the energy to get going in ME/CFS. That lapse in protection allowed toxic bacteria to persist in the bloodstream in people with ME/CFS.
• The findings suggested, then, that a metabolic breakdown that hobbled the early immune response allowed high levels of bacteria to persist in the bloodstream of people with ME/CFS after exercise. That produced a condition called “endotoxemia” whose symptoms (fatigue, cognitive changes, headache, nausea, increases in heart rate, and decreases in blood pressure) bear some similarity to ME/CFS.
• More study needs to be done, but Dr. Alaedini proposed that if his hypothesis is shown to be true immunomodulatory agents, inhibitors of intestinal barrier dysfunction, or drugs that reverse the observed metabolic dysfunction could be helpful.
• Dr. Alaedini is currently attempting to secure funding in three areas: exploring defects in gut barrier function and gut immune response, developing an animal model that mimics the gut-immune-metabolic dysfunction they identified, and exploring the gut-immune-metabolic axis in post-infection syndromes such as long COVID and Lyme disease.

If metabolic problems are the driving force behind the IL-10 upregulation, the inhibited immune response to gut bacteria in the bloodstream, endotoxemia, and possibly neuroinflammation, what would be the next steps in figuring out what the metabolic problems are – and how to solve them?


Metabolic defects appear to be contributing to the dysfunction in the immune response to bacterial translocation and endotoxemia through the mechanism we describe in the paper. However, we believe that the root cause of the endotoxemia lies in gastrointestinal dysfunction.

Our data point to multiple potential therapeutic targets for ME/CFS to explore at the levels of metabolic, immune, and gut barrier function. Several previous studies have identified mitochondrial abnormalities in ME/CFS (which may underlie the metabolic dysfunction and energy deficits).

To move forward, we need better-controlled human studies and relevant animal models to replicate prior studies and better understand if and how they might contribute to ME/CFS symptoms. In other words, we need studies directed at delineating the cause-and-effect relationship between the observed metabolic dysfunction on the one hand and the ME/CFS-associated symptomatic response on the other.

These may include characterizing the potential genetic and proteomic underpinnings of the observed metabolic deficits, the integrity of the gut barrier function at the cellular and molecular level, and the mucosal immune response at the cellular and molecular level (both adaptive and innate).

What are your next moves? Have you tried to get a larger study funded, and if so, how did that go? Are you doing any other work on ME/CFS or related diseases?

We are currently seeking more funding for studies in three areas in particular. One is to focus on the gastrointestinal system and specifically on the defects in gut barrier function and gut immune response in ME/CFS through the direct study of the gastrointestinal tract in patients (i.e., going far beyond just blood work). As part of this, we’re also seeking to understand the relevance of food sensitivity/intolerance, given its high prevalence among ME/CFS patients.

Additionally, we would like to develop an animal behavioral model that recapitulates the specific gut-immune-metabolic dysfunction that we’ve identified in ME/CFS patients in our recent study. The development of a relevant animal model of ME/CFS may greatly advance our understanding of ME/CFS and aid in the development of therapeutics.

 

[Murph]

An animal model would be wonderful. Once we were able to give mice or rabbits mecfs science will go faster.

Even doing it the hard way is probably a good idea: infect a bunch of lab animals with a bunch of viruses and see if any of them never seem to get better. Rinse and repeat that until you can find a combo that develops an me/cfs like illness reliably. Even just being able to observe the illness develop could tell us what to look for in people, maybe find a biomarker. But then the real value would be having a model we could experiment on.

 

[Wishful]

An animal model would be wonderful.

Kind of hard to do. We can't even prove that a human has ME, so how can we prove that an animal has it? You might get some mice or bunnies who appear lethargic and don't do well on mazes, but is that ME or something else?

 

[Aidan Walsh]

I cannot see how all of this fits in with blocked veins in the stomach, one Woman diagnosed with Nutcracker Syndrome MALS MSAS Pelvic Vein Compression APS & another the same with latent TB who was treated & also had the kidney removed after a failed vein AT Auto Transposition at 3 months which sent her back to Emergency with high blood pressure 220, pressure in the eyes & massive headaches.

My left kidney is enlarged it is also lopsided one Urologist suggested a Congenital kidney. No one is doing the proper gold-standard testing Doppler color ultrasound, Venous abdominal/pelvis Scans & proteinuria urine supine 8 hours & 16 hours upright collections & microscopic blood in the urine test

I have no doubts I was Born with this damn condition. Call it ME/CFS EDS Lymies its vascular issues 100% & the kidney offers nutrition to the body. 'I can assure you there is nothing wrong with your kidney' is the Author Doctor/GP/Med Student below the first pdf even the NIH posted her paper publication, she was also labelled as FND

 

[bertiedog]

I think I have found a researcher who understands what exactly happens to cause this breakdown in our colon and especially the gut barrier which the above article is also talking about.

https://www.lucymailing.com/the-oxy...N4m3C2iSGGmsDJDTgMVNusdWuNECm8UVT7bOhx9cG4glw

She mentions a lot of research to back up her statements although admittedly many of the studies are on rats and mice. To me I think this article is HUGE in what it says - about the low level of good or obligate bacteria that are found in compromised guts of people with this problem and has been found in ME (and many other illnesses too) plus the excess number of pathogenic or faculative bacteria as a result of this process. Proteobacteria and Enterobacteria which are part of the Proteobacteria genera will be the result. (I have got loads of them as my recent Biomesight test proves).

We end up with very little if any of Butyrate which is ESSENTIAL to the normal function of the colonocytes in the gut and especially the gut lining. She explains that the gut should be in a state of hypoxia to be healthy because the good bacteria can only survive in a hypoxic state. However the pathogenic bacteria can survive in the presence of oxygen in fact they thrive and hugely outnumber the good bacteria causing the breakdown in our colon and the epithelial cells.

When I came across the explanation of how these pathogenic bacteria like E Coli, Klebsiella, Citrobacter, etc can also steal GLUCOSE from our body and the result is high lactate and nitrate levels which have been found in ME (at least the high lactate has been). All of this affects are energy levels because these bacteria all produce toxins. My own experience is that unstable glucose levels have been a big problem for me for years no matter how carefully I eat and this is the first explanation of why I might experience this.

Obviously Lucy's explanation is fully researched with many examples of findings in studies but I couldn't quite believe what I was reading because it completely explained how I got into the situation of ME in 2000, two years after I had a bad case of Campylbactor poisoning, a known pathogen that damages the working of a healthy gut (there are studies to prove Salmonella does this too plus some other things like the use of ANTIBIOTICS and a low fibre diet),

It is a long read and quite technical but I was blown away by her explanations. I should say I have no connection to Lucy M, the only way I learned about this was from the Facebook Hydrogen Sulphide SIBO Support group.

Pam

 

[Wishful]

although admittedly many of the studies are on rats and mice.

Yes, that doesn't necessarily translate to human guts/microbiomes.

We end up with very little if any of Butyrate which is ESSENTIAL to the normal function of the colonocytes in the gut and especially the gut lining.

Well, I spent the last year or so on a low-fibre diet, and while my baseline symptoms were worse than before this intolerance, it wasn't a huge increase, despite having little butyrate production. I can accept microbiome problems worsening ME symptoms, but I don't feel that they are a core part of ME. Besides, if it was that simple, there should be more reports of people having severe symptoms from low-fibre diets and more reports of amazing success from butyrate supplementation. Hmmm, I suppose you could count my recent success with probiotics as supporting evidence, although not proof of the theory.

Hopefully some people will read that article and try the suggested treatments and report the results.

 

[bertiedog]

Yes, that doesn't necessarily translate to human guts/microbiomes.

Actually there were many studies on humans mentioned especially as to the cause of the gut dysfunction. I think it was where Lucy was looking into further research for further explanations to get a fuller understanding of why the depletion was happening after say poisoning with Campylbacter as happened in my case.

What I feel is that I think it is has become obvious that there are likely subsets of ME sufferers, not everybody is the same so perhaps this explanation only applies to some of us though I think it is highly likely that any ME sufferer, if they do testing via 16S they would find that they also had this issue. It has definitely been reported that ME sufferers have low short chain fatty acids especially butyrate which is essential to the function of the gut barrier. Apparantly nothing else can compensate for this unless one supplements high dose butyrate after the infection has occurred. I think they are still researching whether you can reverse the breakdown of the gut barrier if high dose butyrate is supplied. From my experience I don't think it can but I don't supplement really high doses.

I can see how toxins leaking from the gut into the blood stream is going to cause immune dysfunction because these toxins aren't supposed to be in the blood stream at all. We shouldn't be producing endotoxins at all but some of us definitely are!

Pam

 

[Aidan Walsh]

Yes, that doesn't necessarily translate to human guts/microbiomes.


Well, I spent the last year or so on a low-fibre diet, and while my baseline symptoms were worse than before this intolerance, it wasn't a huge increase, despite having little butyrate production. I can accept microbiome problems worsening ME symptoms, but I don't feel that they are a core part of ME. Besides, if it was that simple, there should be more reports of people having severe symptoms from low-fibre diets and more reports of amazing success from butyrate supplementation. Hmmm, I suppose you could count my recent success with probiotics as supporting evidence, although not proof of the theory.

Hopefully some people will read that article and try the suggested treatments and report the results.

Maybe it is the lactic acid D test Avenger had done & got well with a low carbs fiber/no fiber, antibiotics with baking soda combined. He is in remission now

 

[kangaSue]

A somewhat similar type of gut barrier dysfunction can be caused by the likes of methamphetamine or cocaine, by inducing GI tract vasoconstriction a.k.a. chronic intestinal ischemia.
https://www.frontiersin.org/articles/10.3389/fmed.2022.783121/full

I cannot see how all of this fits in with blocked veins in the stomach

Several of the abdominal vascular compression syndromes (NCS, MALS, SMA Syndrome and May-Thurner Syndrome) can all be a cause of such GI tract vasoconstriction too but the mechanisms of how and why aren't well elucidated.

 

[Aidan Walsh]

The best YouTube video I saw was on The Girl with SMA Syndrome---Discovery Channel---Banijay Science from 4 years ago...

Her heart was failing her she underwent 8 hours of Surgery they also told her she had IBS and then anorexia.

She saw a specialist Radiologist she drank barium for an upper GI series tests showed her compression between SMA & the aorta, it can also come between the aorta & spine her kidney vein was blocked.

Another name used is Nutcracker Syndrome...

 

[kangaSue]

Another name used is Nutcracker Syndrome...

Yes, I'm diagnosed with Nutcracker Syndrome. Also chronic mesenteric ischemia but none of the tests I've had done can pinpoint any other reason for the intestinal ischemia. An issue of transient SMA Syndrome may also be part of my picture but the 'upright' component of a barium swallow test has not been done correctly to 100% rule out SMAS too.

 

[Aidan Walsh]

Yes, I'm diagnosed with Nutcracker Syndrome. Also chronic mesenteric ischemia but none of the tests I've had done can pinpoint any other reason for the intestinal ischemia. An issue of transient SMA Syndrome may also be part of my picture but the 'upright' component of a barium swallow test has not been done correctly to 100% rule out SMAS too.

I see so many patterns now some have SMA/Aorta others have Aorta/Spine compressions. Has anyone ever looked for a Gist tumor in you it can act like NC or SMA? A YouTube video called 13-year Mystery Solved---Mystery Diagnosis it was part 1 or it comes up also as The Stomach Ache she had a Gist Tumor.

Did you have any Surgeries thus far for NC? I had an incisional hernia that fixed the hernia but never stopped my left swelling lower rib stomach area & sharp kidney pains & it is enlarged my left kidney.

Some have Pelvic compression syndrome, one said the veins were like sausages in size

 

[Murph]

I think I have found a researcher who understands what exactly happens to cause this breakdown in our colon and especially the gut barrier which the above article is also talking about.

https://www.lucymailing.com/the-oxy...N4m3C2iSGGmsDJDTgMVNusdWuNECm8UVT7bOhx9cG4glw

She mentions a lot of research to back up her statements although admittedly many of the studies are on rats and mice. To me I think this article is HUGE in what it says - about the low level of good or obligate bacteria that are found in compromised guts of people with this problem and has been found in ME (and many other illnesses too) plus the excess number of pathogenic or faculative bacteria as a result of this process. Proteobacteria and Enterobacteria which are part of the Proteobacteria genera will be the result. (I have got loads of them as my recent Biomesight test proves).

We end up with very little if any of Butyrate which is ESSENTIAL to the normal function of the colonocytes in the gut and especially the gut lining. She explains that the gut should be in a state of hypoxia to be healthy because the good bacteria can only survive in a hypoxic state. However the pathogenic bacteria can survive in the presence of oxygen in fact they thrive and hugely outnumber the good bacteria causing the breakdown in our colon and the epithelial cells.

When I came across the explanation of how these pathogenic bacteria like E Coli, Klebsiella, Citrobacter, etc can also steal GLUCOSE from our body and the result is high lactate and nitrate levels which have been found in ME (at least the high lactate has been). All of this affects are energy levels because these bacteria all produce toxins. My own experience is that unstable glucose levels have been a big problem for me for years no matter how carefully I eat and this is the first explanation of why I might experience this.

Obviously Lucy's explanation is fully researched with many examples of findings in studies but I couldn't quite believe what I was reading because it completely explained how I got into the situation of ME in 2000, two years after I had a bad case of Campylbactor poisoning, a known pathogen that damages the working of a healthy gut (there are studies to prove Salmonella does this too plus some other things like the use of ANTIBIOTICS and a low fibre diet),

It is a long read and quite technical but I was blown away by her explanations. I should say I have no connection to Lucy M, the only way I learned about this was from the Facebook Hydrogen Sulphide SIBO Support group.

Pam

That was an interesting read. I find it all quite plausible. Lots of us have IBS symptoms. I did a hydrogen breath test once and I have just about the most savage case of fodmap-sensitivity they can measure. I haven't eaten onions in years!

Obviously the gut is supposed to help regulate the microbiome but can't. excess oxygen and "capture" of endothelial cells by bad bugs is a credible explanation.

My experience is that if I eat a lot of fibre my symptoms worsen; the explanation I use is that in a population of bad bugs, fibre feeds the bad bugs as much as the good. I can eat fibre, just not too much. Fodmaps I feel are probably even worse. I can trigger PEM via eating fodmaps, and my theory on that is I get gut leakage causing LPS in the bloodstream.

I'd love to revert my gut bugs to a healtheir population and I've spent a lot of money on probiotics over the years. They help but only temporarily. I guess now I'm going to try butyrate!

 

[kangaSue]

I see so many patterns now some have SMA/Aorta others have Aorta/Spine compressions. Has anyone ever looked for a Gist tumor in you it can act like NC or SMA?

I'm well screened for tumours having had a lung cancer diagnosis at one point and surgery for that.

Did you have any Surgeries thus far for NC

Some have Pelvic compression syndrome, one said the veins were like sausages in size

Pelvic compression syndrome goes with NC in about 80% of cases (in women at least) so that's something else I have too in having a 'massively dilated left ovarian vein'. I'm not offered any help for NS by way of surgery because I don't have any significant debilitating left flank pain from it.

 

[bertiedog]

That was an interesting read. I find it all quite plausible. Lots of us have IBS symptoms. I did a hydrogen breath test once and I have just about the most savage case of fodmap-sensitivity they can measure. I haven't eaten onions in years!

Obviously the gut is supposed to help regulate the microbiome but can't. excess oxygen and "capture" of endothelial cells by bad bugs is a credible explanation.

My experience is that if I eat a lot of fibre my symptoms worsen; the explanation I use is that in a population of bad bugs, fibre feeds the bad bugs as much as the good. I can eat fibre, just not too much. Fodmaps I feel are probably even worse. I can trigger PEM via eating fodmaps, and my theory on that is I get gut leakage causing LPS in the bloodstream.

I'd love to revert my gut bugs to a healtheir population and I've spent a lot of money on probiotics over the years. They help but only temporarily. I guess now I'm going to try butyrate!

I take a few targetted strains of probiotics along with polysaccharides like Artichoke powder, pomegranate peel and cinnamon powder (have to be careful with the pommegranate one because it can be very constipating which is the last thing I need) plus FOS in varying amounts. I don't seem to tolerate Bimuno which is nothing feeder of butyrate providing bacteria, it gives me diarrhoa probably because of the lactose content.

If tolerated FOS is an excellent feeder of the butyrate producing bacteria but I started very low and slow but now do fine on up to 8g at a time, sometimes twice daily. I think this has helped to improve my gut transit time together with the butyrate I have been taking for the past 3 months. Actually I have just switched to Tributyrate that Lucy Mailing recommends but it is a lot more expensive so will just give it a month to see if I think there are any other beneficial changes from my usual sodium butyrate.

The probiotics I am taking and also using to make my own yoghurt are Lactobacillus Rhamanous GG, Bifidobacteria Lactis HN019 and Bifidobacteria Longum BB536. All these have documented benefits for the gut. The last 2 are from the Life Extension range and the Rhamanous is one from Amazon.

What I have learned from the 2 gut groups I belong to on Facebook is that it can take a long time for changes to take place using these natural methods but my bowel habit has improved with almost normal bowel movements on some days plus the colour is more normal too (used to be a very unpleasant colour. (Sorry about that, might be too much information!). One benefit has been that the brain fog has lifted for quite a lot of the time, still there first thing.

I am going to retest with Biomesight in the New Year so I can make comparisons with last July.

Good luck with your gut issues, it really is a difficult problem to solve especially for ME sufferers I think.

Pam

 

[Murph]

I followed through on my pledge to buy butyrate.

I'd love to revert my gut bugs to a healtheir population and I've spent a lot of money on probiotics over the years. They help but only temporarily. I guess now I'm going to try butyrate!

Two reasons:
I restarted probiotics and the difference was noticeable and immediate. I really should never stop taking them!
I also did some reading that showed sodium butyrate can have some useful effects. https://pubmed.ncbi.nlm.nih.gov/?term="sodium butyrate"&filter=datesearch.y_5&sort=date

I'm planning to do a real push on gut health in early 2024: probiotics, butyrate, resistant starch, fermented foods, and no more crappy processed foods (this is easy for me when I"m on keto, but hard when I eat carbs, the trick wll be sticking to quality carbs like brown rice.). See if I can make a difference in my symptoms.

 

[bertiedog]

I followed through on my pledge to buy butyrat

As you know I am learning so much about the gut and its proper function and how things like bile acids play a part as well as you have said butyrate. I have now been on a different form of butyrate which has evidence for more activity in the gut than sodium butyrate. Its 3 weeks almost that I have been taking 2 Tributyrin and I haven't had one bout of diarrhoea during that time which is unheard of for me for maybe the past few years at least.

I don't know what your main gut issue is but mine basically has been daily constipation with a few days when everything goes in the other direction, namely diarrhoea or at least much too loose stools but all the time I have been on this different form of butyrate this hasn't happened and in addition I even get the signal in the mornings that I need to go to pass a stool (hope this isn't too gross but it is difficult to explain otherwise).

Again this hasn't been happening to me for at least the past 2 years, on a daily basis no signal that I neeed to go to pass a stool. Of course I am still carrying on with the prebiotic FOS in varying amounts from 5 g to 8g once or twice daily, plus Pommegranate peel powder but only 1/4 teaspoon because it can be very constipating and also 1/4 teaspoon cinnamon powder plus a large capsule of Artichoke powder as a form of inulin

The probiotics I am taking in addition are Lactobaccilus Rhamanous with my breakfast and also another one which contains 2 other well know strains including Lactobaccilus Acidopholus and at lunch Bifido Lactis HN19 and Bifido Longum BB536.

I have been taking these for probably 2 months now and wasn't noticing any real difference until the Tributyrin although things had changed in that my stool had become a better colour and stools were sometimes formed (gross I know).

I don't eat processed food and haven't for a long time but probably the one exception is a weekly mild curry from a local supermarket with lots of veg and no rice because I found if I added rice it made me more hungry which tbh I never really feel hunger.

My next experiment is with bile acids in low dose plus a supplement called TUDCA which somebody on the Facebook Gut Club group has used to lower his Bilophila Wadsworth, one of the main H2S producers from 5% to 0.5% using both of these but it took a year but he didn't change his diet, the only other thing was he took 650 mg hcl with meals which I also do anyway. 0.5% is top end of normal for Bilophila to have in one's microbiome, because it does some important things in the gut, mine was 0.83% but also I had lots of Proteobacteria which produce LPS which hopefully the TUDCA will help to reduce plus the Tribuytrin.

Hope I haven't confused you with the latest!

Pam

 

[Murph]

As you know I am learning so much about the gut and its proper function and how things like bile acids play a part as well as you have said butyrate.

My next experiment is with bile acids in low dose plus a supplement called TUDCA which somebody on the Facebook Gut Club group has used to lower his Bilophila Wadsworth,

Pam

Interesting on the TUDCA. It is also part of @mariovitali's regimen for recovery, and fits into the new NIH finding on WASF3 overproduction, because it reduces ER stress. I didn't know it was supposed to have gut effects as well.
I bought 60 tablets a few months back and took them and noticed absolutely nothing, but who knows, perhaps I got a dud brand. I might try it again.

 

[Bronc]

An animal model would be wonderful. Once we were able to give mice or rabbits mecfs science will go faster.

Even doing it the hard way is probably a good idea: infect a bunch of lab animals with a bunch of viruses and see if any of them never seem to get better. Rinse and repeat that until you can find a combo that develops an me/cfs like illness reliably. Even just being able to observe the illness develop could tell us what to look for in people, maybe find a biomarker. But then the real value would be having a model we could experiment on.

Ethically speaking I would not want any bio marker that had been tested on animals. This summary from PETA explains why testing medical products designed for humans on animals is not fit for purpose:

"The most significant trend in modern research is the recognition that animals rarely serve as good models for the human body. Human clinical and epidemiological studies, human tissue- and cell-based research methods, cadavers, sophisticated high-fidelity human-patient simulators, and computational models have the potential to be more reliable, more precise, less expensive, and more humane alternatives to experiments on animals. Advanced microchips that use real human cells and tissues to construct fully functioning postage stamp–size organs allow researchers to study diseases and also develop and test new drugs to treat them. Progressive scientists have used human brain cells to develop a model “microbrain,” which can be used to study tumors, as well as artificial skin and bone marrow. We can now test skin irritation using reconstructed human tissues (e.g., MatTek’s EpiDermTM), produce and test vaccines using human tissues, and perform pregnancy tests using blood samples instead of killing rabbits.

Experimentation using animals persists not because it’s the best science but because of archaic habits, resistance to change, and a lack of outreach and education.''

 

[LINE]

My ME accelerated with a pathogenic invasion in the gut which after multiple trials of antibiotic substances, has proven to be a resistant organism or I should say virulent as it has been reduced. Gut permeability is a major issue which is closely linked to inflammatory processes.

Obviously, the microbiome changes during these immune events, recent studies have shown the imbalance that is created during these events. SCFA (short chain fatty acids - example butyrate) becomes diminished which leads to more inflammation. Organisms (anerobic bacteria) that produce SCFAs are difficult to grow in the hostile environment. So, the cycle persists.

The microbiome environment is much more complex than recognized. Fermented foods have proven to be a better choice for me versus probiotics. Binders, which absorb toxins (toxins created by immune reactions) have always helped me. Rich polyphenols are another big plus.