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Dr. Chia's stomach biopsy

Messages
13
I'm still kind of confused as to whether I have a messed up immune system that allowed for this chronic infection, or this infection messed up my immune system.

I'm also not sure if I should be happy that I found something that can be potentially treated, or saddened that it's something that I can't find any success stories about. Seems like enterovirus is almost a sentencing to feeling sick forever. I also have autoimmune tendencies, so I don't know if I will be able to ever take enough Eqillibrant to fully eradicate the virus
 

Hip

Senior Member
Messages
17,870
I don't think there is really any solid information on this. As far as I know these are not tests of generally recognised value. Having spent several years working with immunostaining of this sort I would be concerned about staining patterns in areas like this, which are often due to non-specific binding. I personally don't think I would base any clinical decisions on these findings.


According to one of Dr Chia's papers:
5D8/1 mAb has been used by a number of investigators to detect a common enteroviral protein in the tissues of infected animals and human tissues, and the specificity has been correlated with viral genome detection or culturable viruses.22–25

One of the refs is this one:
Evaluation of an enterovirus group-specific anti-VP1 monoclonal antibody, 5-D8/1, in comparison with neutralization and PCR for rapid identification of enteroviruses in cell culture
This study found:
There was total agreement between the results obtained with the MAb and those obtained by PCR, even for those strains of enteroviruses which were found to be untypeable with polyclonal antisera. These data demonstrate the usefulness of the MAb for rapid identification of enteroviruses in cell culture.
 

halcyon

Senior Member
Messages
2,482
Did the Equilibrant not help at all with symptoms outside the gut?
Those were just the first symptoms I noticed improving. I only took it by itself for a few months and then added in antivirals so I am not able to directly ascribe improvements to any one thing at this point.
 

Hip

Senior Member
Messages
17,870
I'm still kind of confused as to whether I have a messed up immune system that allowed for this chronic infection, or this infection messed up my immune system.

The answer to that question nobody knows, but it has been discussed on this forum from time to time.


My hunch is that it may be the robustness of immune response at the time of contracting an acute enterovirus infection that plays a major role in determining whether or not that infection becomes chronic and leads to ME/CFS.

I got this idea from Dr Chia's observation that people inadvertently given corticosteroids (which tone down the immune response) during the time of an acute viral infection have a higher risk of developing ME/CFS. Chia says he sees lots of ME/CFS patients who have this medical history of corticosteroids given during acute infection.

It seems that acute infection + corticosteroids is almost a recipe for creating ME/CFS.

My feeling is that if the immune response is weak and inadequate during the fierce initial acute viral infection, then the virus may penetrate deeper into the body, breaching into tissue compartments such as the central and peripheral nervous system, and then once the virus has insinuated itself into these compartments, it both triggers ME/CFS and also becomes harder to eradicate. Three brain autopsies performed on ME/CFS patients found enterovirus infection in the brain tissues.

I have also speculated that if the immune response is weak and inadequate, it may allow the virus to enter and infect important immune organs such as the thymus (coxsackievirus B4 can infect the thymus), or important immune cells such as B-cells (in mice, acute coxsackievirus B has been shown to infect up to 10% of B-cells). Then once this happens, it may weaken the immune system or render it dysfunctional, such that it now has difficulty clearing enterovirus from the body.

As we were discussing just a few days ago, it is interesting that in males, oxymatrine can lead to permanent improvements in ME/CFS (improvements that hold even after stopping oxymatrine), which suggests some hysteresis is going on: ie, that with a severe enterovirus infection, the infection itself might weaken the immune system and thus prevent viral clearance; but once that infection is reduced with oxymatrine, the immune system weakening is abated, and so thereafter, the immune system can better keep the virus in check.



As an aside: I wonder whether it might be possible to create a mouse model of ME/CFS by exposing mice to enterovirus while they are given corticosteroids. If we could create ME/CFS in mice, that might be tremendously useful for research purposes.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I'm still kind of confused as to whether I have a messed up immune system that allowed for this chronic infection, or this infection messed up my immune system.

I'm also not sure if I should be happy that I found something that can be potentially treated, or saddened that it's something that I can't find any success stories about. Seems like enterovirus is almost a sentencing to feeling sick forever. I also have autoimmune tendencies, so I don't know if I will be able to ever take enough Eqillibrant to fully eradicate the virus

If this is found in a significant minority of healthy people and has not been replicated by other groups then it seems to me that it is something entirely compatible with getting completely well, so no sentence to anything.
 

JES

Senior Member
Messages
1,323
Enteroviruses and gut inflammation have been associated with Type 1 diabetes as well (ref). I'm still baffled why this isn't top priority, or at least a priority in CFS/ME reserach. All it takes is for somebody to replicate the results of Dr. Chia, but none seems interested. I'm afraid the 10 years of research from Chia will soon be forgotten unlesss someone else picks up his work. At least scanning for enterovirus infection in CFS/ME patients would fit this recent big data-driven research well, it would tell us whether there is a real link between the two.

Besides, treating enterovirus infections would be much simpler than immune cell depleting therapies, assuming that an effective antiviral medication was found. Even if the enterovirus itself isn't the causative/driving factor of CFS/ME, it might attribute to a significant part of symptoms in some people.
 

Hip

Senior Member
Messages
17,870
I'm still baffled why this isn't top priority, or at least a priority in CFS/ME reserach. All it takes is for somebody to replicate the results of Dr. Chia, but none seems interested.

I totally agree, it so frustrating that researchers cannot see the elephant in the room.


In any case, Dr Chia's research itself replicated the numerous studies performed in the 1980s and 1990s in the UK, which found enterovirus in the muscle biopsies of ME/CFS patients. So there is a great deal of evidence for enterovirus association in ME/CFS.

The only difficultly with enterovirus research is that in chronic infections, enterovirus tends to be found in the tissues rather than the blood, so this is why tissue biopsies are used. Originally the British researchers used muscle tissue biopsies to detect enterovirus in ME/CFS patients, and found that a lot more ME/CFS patients had enterovirus infections in their muscles than healthy controls.

I believe the reason Dr Chia switched to taking stomach tissue biopsies rather than the muscle tissue biopsies is because the former is painless (and thus more amenable to routine clinical use), whereas muscle biopsies can very painful afterwards, and leave a scar.

So it was something of an innovation by John Chia to switch to stomach biopsies instead of muscle biopsies. It made routine tissue testing for enterovirus relatively easy to do.



But what we really need is some new testing procedure that can easily and non-invasively detect the presence of enterovirus infection of the tissues. It's hard to detect chronic enterovirus infections, because in chronic infections, this virus lives hidden inside human cells, as a smoldering intracellular infection.
 

Thomas

Senior Member
Messages
325
Location
Canada
I totally agree, it so frustrating that researchers cannot see the elephant in the room.
It appears that on @Patrick* Blog that the CDC attempted to replicate Dr. Chia's findings but were not successful in their attempts. In the comments section someone asks if they were even able to see what Dr. Chia sees in his lab but there doesn't appear to be a clear answer. I tend to lean on the enteroviral hypothesis for ME to be a much stronger one than any other viral or retroviral theory -- mostly due to the notion that only enterovirus have the appropriate incubation period time to initiate an outbreak of ME whereas other viruses' incubation periods are much longer.

Here's the blog post. Perhaps the author has some further insights:
http://quixoticmeblog.blogspot.com/2016/01/dr-c-on-hunt-again.html#comment-form
 

Hip

Senior Member
Messages
17,870
the CDC attempted to replicate Dr. Chia's findings but were not successful in their attempts.

Yes, I read that on Patrick's blog, but don't know what to make of it.

For a start, after Dr Chia sent his biopsy samples to the CDC, the CDC left them hanging around for over a year before they bothered to even look at them. That does not suggest they actually had much interest in this. And it may also mean the samples were too old by the time the CDC got to look at them.

Then the CDC did not publish any info about their testing methodology, so we cannot scrutinize their results. And finally when Dr Chia suggested to the CDC that they test again with a more sensitive technique, the CDC declined. Again, it seems to show a lack of interest on the part of the CDC.


It's also interesting that in the case of Morgellons disease, some researchers found Borrelia in the skin lesions of Morgellons patients, and published this. But when the CDC commissioned a major examination of Morgellons patients, they found nothing. So you wonder just how good the CDC are at detecting pathogens.



I found this interesting from the same article you linked to:
RNA Sequencing of Samples

In recent years, Dr. C has also been working with a biologist from Cornell University. He sent the Cornell researcher a portion of his stomach biopsies, some from moderate patients and others from more severely ill patients. Rather than look for enteroviruses, the Cornell researcher took the novel approach of sequencing the RNA in the samples. She started with the samples from moderately ill patients and apparently the patterns she found were unusual. (The question of what exactly was unusual about the samples was apparently too complicated to explain to me, a lay person, in the context of a doctor's appointment. I of course understand.) Dr. C is anxiously awaiting the results of the sequencing for the samples from severely ill patients. He seemed to think this could be a breakthrough.

Vagus Nerve Research

Dr. C also mentioned some fascinating research from a Danish group of scientists involving the Vagus nerve. In decades past, doctors sometimes resorted to severing the Vagus nerve of patients who presented with persistent and otherwise untreatable stomach ulcers. (Thankfully, we no longer treat ulcers this way.) But as a result, there is a significant population with severed Vagus nerves, which offers an opportunity to study the role of the Vagus nerve in overall health.

Some patients with Parkinson's acquire the disease in sudden onset fashion, after suffering severe flu-like symptoms. (Sound familiar?) There is a much lower incidence of Parkinson's disease in people whose Vagus nerves have been cut. The Danish team believes this is because Parkinson's is sometimes caused by either Enterovirus 71 or Coxsackie B - 4, which enters the body through the stomach and travels from the stomach to the brain via the Vagus nerve, bypassing the blood-brain barrier. The Danish team will publish their evidence soon.

For years, Dr. C has looked for evidence that enteroviruses migrate from the stomach to the brain via the blood. He never quite found the evidence he was looking for. He believes the Vagus nerve possibly makes more sense as the vehicle by which the virus travels from the stomach to the brain.
 

Thomas

Senior Member
Messages
325
Location
Canada
That's really interesting. Your further insight as to the way the CDC managed this project lends me to believe this was a tremendously low priority for them. It would therefore make more sens as mentioned in a previous post to try and get current ME researchers to attempt to reproduce these findings or to find other ways to confirm enteroviral involvement.

The vagus nerve is definitely a big deal in ME in my opinion. Even as a teen and 20 something (a decade before ME) with anxiety and classic anxiety related IBS - it was the vagus nerve that was at the center of attention of the Naturopath community. My conventional doctor at the time wasn't too interested in its potential role.
 

Hip

Senior Member
Messages
17,870
Your further insight as to the way the CDC managed this project lends me to believe this was a tremendously low priority for them.

I really am just guessing about what happened at the CDC, based on Patrick's blog. From what I read, does not seem like the CDC are that interested. If they were, they could have even obtained their own stomach biopsy samples, fresh taken from ME/CFS patients. The procedure to take a stomach biopsy sample is very straightforward, and any gastroenterologist can do it.

As you say, it probably would be better to get other ME/CFS researchers and university departments to attempt to replicate Dr Chia's findings. Even in the UK, Canada or Australia, researchers could attempt to replicate. I cannot understand why they don't.
 

TigerLilea

Senior Member
Messages
1,147
Location
Vancouver, British Columbia
As you say, it probably would be better to get other ME/CFS researchers and university departments to attempt to replicate Dr Chia's findings. Even in the UK, Canada or Australia, researchers could attempt to replicate. I cannot understand why they don't.

I don't know much about enteroviruses but the little I did read implied that it was mostly children who got them. Possibly this is why no one else seems to be interested in pursuing this in relation to CFS/ME. Most of the info I found on chronic enteroviruses in relationship to CFS/ME all seemed to lead back to Dr. Chia. That always raises a red flag for me as to how legit this theory is.
 

Hip

Senior Member
Messages
17,870
the little I did read implied that it was mostly children who got them.

Children do get a lot of enterovirus infections, but they strike adults too. In fact, it may turn out that enteroviruses are a leading cause of sudden fatal heart attacks in adults, as it has been found that 40% of patients who died suddenly from myocardial infarction have post-mortem evidence of enteroviral infection in their hearts.

The virus that triggered my ME/CFS was most likely coxsackievirus B, and I observed that as this enterovirus spread to friends and family, it caused 3 heart attacks out of the blue in three previously healthy adults.



Most of the info I found on chronic enteroviruses in relationship to CFS/ME all seemed to lead back to Dr. Chia.

Dr Chia has done a lot research on chronic enterovirus infection in ME/CFS over the last 10 or 15 years, but lots of other researchers dating back to the 1970s have also investigated enterovirus infections in ME/CFS patients. Many of these early research papers are listed in this post. Out of all the viruses associated with ME/CFS, there are far more studies linking enterovirus to this disease than any other virus.

Acute and chronic enterovirus infections are also linked to other diseases. Professors Nora Chapman and Steve Tracy are investigating chronic enterovirus infections in chronic myocarditis and dilated cardiomyopathy (two inflammatory conditions of the heart muscle). Myocarditis and dilated cardiomyopathy are the cause of around 45% of heart transplants in the United States. Ref: 1

Chapman and Tracy and many others around the world are investigating the enterovirus infections found in type 1 diabetes (enterovirus chronically infects the insulin-producing beta cells of the pancreas); it could be that enterovirus is a cause of T1D, but at this stage this remains undetermined.

Chronic enterovirus infections has also been found in Crohn's disease, among other diseases.
 

jepps

Senior Member
Messages
519
Location
Austria
I don't know much about enteroviruses but the little I did read implied that it was mostly children who got them. Possibly this is why no one else seems to be interested in pursuing this in relation to CFS/ME. Most of the info I found on chronic enteroviruses in relationship to CFS/ME all seemed to lead back to Dr. Chia. That always raises a red flag for me as to how legit this theory is.

This study shows a correlation between chronic gut infection and coxsackie viruses:

The results showed significant amounts of enteroviruses in the intestines of all of the children with Crohn´s disease, whereas the control group had no or only minimal amounts of enteroviruses in their intestines. Similar results were obtained using two different methods. Enteroviruses were found not only in intestinal mucous linings but also in so-called nerve cell ganglia in deeper segments of the intestinal wall. Receptors for a group of enteroviruses were also found in both the intestinal mucous linings and nerve cell ganglia, which may explain how the virus can make its way into the nerve system in the intestine.

Comparing with this review paper about the role of the intestinal virome as permanent trigger for chronic inflammation in the gut in CFS/ME,

It is likely that ME/CFS follows a non-classical autoimmune mechanism and it has been long described to encompass idiopathic immune dysregulation. Based upon the evidence presented in this review, a candidate for chronic stimulation of the immune system that triggers autoimmune processes may be found in the intestinal virome.

Of particular interest are the viral components of the microbiota. Components of the virome, specifically bacteriophages, which make up 90% of the gut virome composition [125] are primary drivers of bacterial diversity and influence community structure by both eliminating and introducing traits to their host species via the horizontal transfer of genes
 
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jepps

Senior Member
Messages
519
Location
Austria
According to this study, chronic gut inflammation means low diversity of bacteria, and high diversity of viruses.

https://source.wustl.edu/2015/01/viruses-may-play-unexpected-role-in-inflammatorybowel-diseases/
Inflammatory bowel diseases are associated with a decrease in the diversity of bacteria in the gut, but a new study led by researchers at Washington University School of Medicine in St. Louis has linked the same illnesses to an increase in the diversity of viruses.

Despite we have a high level of many viruses, perhaps enteroviruses are on the root of the problem, as they infect the intestine, and therefore create a chronic condition of inflammation and dysbiosis.
 
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Messages
38
The answer to that question nobody knows, but it has been discussed on this forum from time to time.


My hunch is that it may be the robustness of immune response at the time of contracting an acute enterovirus infection that plays a major role in determining whether or not that infection becomes chronic and leads to ME/CFS.

I got this idea from Dr Chia's observation that people inadvertently given corticosteroids (which tone down the immune response) during the time of an acute viral infection have a higher risk of developing ME/CFS. Chia says he sees lots of ME/CFS patients who have this medical history of corticosteroids given during acute infection.

It seems that acute infection + corticosteroids is almost a recipe for creating ME/CFS.

My feeling is that if the immune response is weak and inadequate during the fierce initial acute viral infection, then the virus may penetrate deeper into the body, breaching into tissue compartments such as the central and peripheral nervous system, and then once the virus has insinuated itself into these compartments, it both triggers ME/CFS and also becomes harder to eradicate. Three brain autopsies performed on ME/CFS patients found enterovirus infection in the brain tissues.

I have also speculated that if the immune response is weak and inadequate, it may allow the virus to enter and infect important immune organs such as the thymus (coxsackievirus B4 can infect the thymus), or important immune cells such as B-cells (in mice, acute coxsackievirus B has been shown to infect up to 10% of B-cells). Then once this happens, it may weaken the immune system or render it dysfunctional, such that it now has difficulty clearing enterovirus from the body.

As we were discussing just a few days ago, it is interesting that in males, oxymatrine can lead to permanent improvements in ME/CFS (improvements that hold even after stopping oxymatrine), which suggests some hysteresis is going on: ie, that with a severe enterovirus infection, the infection itself might weaken the immune system and thus prevent viral clearance; but once that infection is reduced with oxymatrine, the immune system weakening is abated, and so thereafter, the immune system can better keep the virus in check.



As an aside: I wonder whether it might be possible to create a mouse model of ME/CFS by exposing mice to enterovirus while they are given corticosteroids. If we could create ME/CFS in mice, that might be tremendously useful for research purposes.
Actually, Dr. Nancy Klimas hits infected mice with corticosteroids to create the mouse model of Gulf War Syndrome. Of course there is no money for a mouse model o ME.
I totally agree, it so frustrating that researchers cannot see the elephant in the room.


In any case, Dr Chia's research itself replicated the numerous studies performed in the 1980s and 1990s in the UK, which found enterovirus in the muscle biopsies of ME/CFS patients. So there is a great deal of evidence for enterovirus association in ME/CFS.

The only difficultly with enterovirus research is that in chronic infections, enterovirus tends to be found in the tissues rather than the blood, so this is why tissue biopsies are used. Originally the British researchers used muscle tissue biopsies to detect enterovirus in ME/CFS patients, and found that a lot more ME/CFS patients had enterovirus infections in their muscles than healthy controls.

I believe the reason Dr Chia switched to taking stomach tissue biopsies rather than the muscle tissue biopsies is because the former is painless (and thus more amenable to routine clinical use), whereas muscle biopsies can very painful afterwards, and leave a scar.

So it was something of an innovation by John Chia to switch to stomach biopsies instead of muscle biopsies. It made routine tissue testing for enterovirus relatively easy to do.



But what we really need is some new testing procedure that can easily and non-invasively detect the presence of enterovirus infection of the tissues. It's hard to detect chronic enterovirus infections, because in chronic infections, this virus lives hidden inside human cells, as a smoldering intracellular infection.
Dr. Komaroff has said that the Chia work needs to be replicated. But NIH told him never to come back to them with an enterovirus related proposal. When Salk announce his polio vaccine thousands of enteroviral researchers headed for the hills. Yet when a few outbreaks in recent years killed some kids researchers went out looking again. there's a lot of enterovirus in them thar hills.
 

Hip

Senior Member
Messages
17,870
Actually, Dr. Nancy Klimas hits infected mice with corticosteroids to create the mouse model of Gulf War Syndrome. Of course there is no money for a mouse model o ME.

You mean she infected the mice with a virus, and at the same time gave the mice corticosteroids, to weaken the immune system and allow the virus to do more damage? Do you know what virus she used, and would have reference for that research please?