XMRV CREB and LEAKY GUT

[Gerwyn]

XMRV binds within CREB genes CREB controls gut permeability

It has been suggested that oxygen free radicals and calcium influx may play a role in the development of endothelial barrier injury, possibly leading to intestinal hyperpermeability [8578176]. Under certain conditions intestinal epithelial cells may become a source of proinflammatory cytokines, which actively contribute to ongoing inflammation through autocrine disruption of epithelial barrier function In gastrointestinal tract, mucosal hypoxia is closely associated with chronic inflammation, and these events are dependent on alterations in the expression and function of CREB, an event regulated mainly through influx of calcium.

so in theory XMRV integration into CREB results in polymorphism in creb/cre protein leading to leaky gut syndrome

 

[guest]

Very interesting, thanks Gerwyn. I hope they take a look into this direction as well.

 

[Frank]

Very interesting! Where did you get this info?

 

[JillBohr]

When looking back at the Dr. Judy Mitkovits newsletter, I remembered the discussion on saliva and how it can be transmitted through other bodily fluids. Of course, how can I not forget when Maarten brought up the "Precious Bodily Fluid Scene" from Dr. Strangelove. I am hoping WPI is looking to see if they can find XMRV is the intestinal tract. I read and reread what Gerwyn wrote above. I have a dear friend that also has a child with autism and she is dying from anal cancer. I had never spoken to her about XMRV but I wonder if I should approach her and see if she would be interested in getting tested. Perhaps antivirals would work better than chemo. Although, would chemo kill XMRV? I have no idea.

 

[omerbasket]

Jill, that's something that interests me too: I have also Crohn's disease - And I remember that when I used to get Methotrexate (a chemo drug that in much larger doses is used to treat cancer patients, as much as I know) injections to treat the Crohn's disease - It seemed that after the first two days, in which I had bad side effects every time I got a shot (and I got a shot once a week), I felt better in every aspect - I think also the fibromyalgia's aspect. So, I think there are a number of possibilities here as to "why?", but I think that one possibilty is that methotrexate does something to XMRV.

Gerwyn and other scientists here: I heard the term "Leaky Gut Syndrome" once, and begun to check what it is. When I found out, it seemed to me as a possibility for things that are going on in my body, since I have Crohn's, but also fibromyalgia, and I think also some kind of IBS. But than I chekced in medical forums in Israel, and I remember that the doctors there said that it's a term from complementary medicine (or do you guys call it "alternative medicine"?). Is leaky gut syndrome a real disease, or is it a thing that has no prove and is only a speculation of the complementary medicine?

 

[Gerwyn]

Jill, that's something that interests me too: I have also Crohn's disease - And I remember that when I used to get Methotrexate (a chemo drug that in much larger doses is used to treat cancer patients, as much as I know) injections to treat the Crohn's disease - It seemed that after the first two days, in which I had bad side effects every time I got a shot (and I got a shot once a week), I felt better in every aspect - I think also the fibromyalgia's aspect. So, I think there are a number of possibilities here as to "why?", but I think that one possibilty is that methotrexate does something to XMRV.

Gerwyn and other scientists here: I heard the term "Leaky Gut Syndrome" once, and begun to check what it is. When I found out, it seemed to me as a possibility for things that are going on in my body, since I have Crohn's, but also fibromyalgia, and I think also some kind of IBS. But than I chekced in medical forums in Israel, and I remember that the doctors there said that it's a term from complementary medicine (or do you guys call it "alternative medicine"?). Is leaky gut syndrome a real disease, or is it a thing that has no prove and is only a speculation of the complementary medicine?

Hi Omerbasket,
The way I use the term relates to hyperpermeability of the epithelium

 

[omerbasket]

Okay, and shortly, what is that (the hyperpermeability of the epithelium) syndrome?

 

[Gerwyn]

Okay, and shortly, what is that (the hyperpermeability of the epithelium) syndrome?

Basically the cells that line the gut walls have a job of keeping certain molecules and ions within the gut and letting others out into the blood.These cells get "poisoned" and stop working as an effective filter so the wrong things get into the gut and the wrong things get out causing chaos with normal gut function bacteria levels and so on.This causes the endocrine systems which regulate things like peristalsis to go kaput and results in more and more inflammation ,pain, lack of oxygen to cells which can die or if really extreme cancerous

 

[omerbasket]

Thanks Gerwin!

 

[julius]

Is leaky gut syndrome a real disease, or is it a thing that has no prove and is only a speculation of the complementary medicine?

The way I understand it, "Leaky Gut Syndrome" is in a similar situation to CFS. There is some good evidence, but it's not accepted and even ridiculed in the mainstream.

Leaky gut (not syndrome), or hyper-permeability is pretty well established as a real phenomenon, though not yet well researched or understood. I think Gerwyn's post is about leaky gut and not the syndrome per se.

 

[Gerwyn]

The way I understand it, "Leaky Gut Syndrome" is in a similar situation to CFS. There is some good evidence, but it's not accepted and even ridiculed in the mainstream.

Leaky gut (not syndrome), or hyper-permeability is pretty well established as a real phenomenon, though not yet well researched or understood. I think Gerwyn's post is about leaky gut and not the syndrome per se.

spot on Julius

 

[natasa778]

There is lots of literature on intestinal permeability in HIV infection that could be relevant, this one here is a decent review:
...However, while many AIDS-defining illnesses could be attributed to loss of mucosal immunity and only become manifest years after acquisition of HIV, many pathological changes, both structural and immunological, occur at the mucosal surfaces from the very onset of HIV infection. In this review we discuss recent studies that have led to a reappraisal of the pathogenesis of HIV disease and how they relate to early studies that documented the structural and functional abnormalities of the HIV-infected GI tract. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777614/?tool=pubmed


Also relevant role of nitric oxide on intestinal hyperpermeability (aka leaky gut):

Cytokine-induced intestinal epithelial hyperpermeability: role of nitric oxide
OBJECTIVE: Incubation of enterocytic monolayers with interferon (IFN)-gamma increases nitric oxide (NO) production and permeability, but NO synthesis inhibitors ameliorate the development of IFN-gamma-induced hyperpermeability. Induction of inducible nitric oxide synthase (iNOS), an isoform of the enzyme responsible for NO biosynthesis, is often enhanced by the synergistic effects of multiple cytokines.... http://www.ncbi.nlm.nih.gov/pubmed/10548215

And NO-activation being mediated by CREB....

 

[natasa778]

"Evidence" of leaky gut in HIV, CFS, autism etc

Is something called bacterial translocation - presence in the blood of products of intestinal pathogens.

Here on the mechanisms:

Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation.
http://www.ncbi.nlm.nih.gov/pubmed/20386714


Bacterial translocation is happening in CFS (also a recent study confirming that to be the case in autism, degree of translocation correlating with severity of disorder), I believe also in MS and many others.

We found that the prevalences and median values for serum IgA against the LPS of enterobacteria are significantly greater in patients with CFS than in normal volunteers and patients with partial CFS. Serum IgA levels were significantly correlated to the severity of illness, as measured by the FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory. The results show that enterobacteria are involved in the etiology of CFS and that an increased gut-intestinal permeability has caused an immune response to the LPS of gram-negative enterobacteria..
http://www.ncbi.nlm.nih.gov/pubmed/17007934

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 http://www.ncbi.nlm.nih.gov/pubmed/19112401

 

[Cloud]

Many things can cause Leaky Gut, including food allergies (esp. Celiac disease), enterviruses, antibiotics, etc. Very interesting to see xmrv added to the mix....This may play into ideas such as Sanjay Shukla's work eventually. I have worked on healing my Leaky Gut problem for a long time now, and have known quite clearly that it plays a major role in my illness......the question that remains for me is what aspects originate upstream vs downstream. It's all coming together rapidly now.

 

[wciarci]

O.K., how do we treat this?

Wendy

 

[Cloud]

O.K., how do we treat this?

Wendy

1). Eliminate the cause .... Pathogens, Poor diet, toxins, drugs, allergens, etc

2). Support healing .... Improve Gut ecology, function, and healing with diet and supplements. I eat a more alkaline diet of primarily fresh whole feeds and roughage. Maximizing GI motility minimizes toxin buildup in the gut which allows GI healing and limits the amount of toxins getting into the blood stream and causing the immune response. In addition to diet, probiotics are good for supporting gut ecology. Also for healing, L-Glutamine is top of the list, but I also use digestive enzymes, Zinc, and sometimes Aloa Vera.

One of the best labs for testing "Intestinal Permeability". They used to mail out the kits upon request....

http://www.genovadiagnostics.com/index.php?option=com_gpanel&Itemid=2&nav=test

 

[julius]

Many of the really good autism docs say they get huge results by simply eliminating whey and gluten.

 

[Jenny]

Has anyone taken the Genova intestinal permability test? Any views on its accuracy?

Jenny

 

[aepalisades]

Genova Diagnostics

I have not used the permiability test however I have taken several of the other tests they offer. They seem more thorough when they perform the stool analyses and find more pathogens and potential stool pathogens than any labs around me- at other labs, my tests come back negative, but I respond well to antibiotics. They aslo test not only antibiotics for resistance and susceptibility to the pathogen, they test some holistic stuff as well.

I highly recommend this lab. I suffered much worse before I found them. The downside was at the time my insurance did not pay well on their tests, but it has been several years. Hope this help, I know it wasn't exactly what you wanted.

Lisa

 

[Cloud]

Has anyone taken the Genova intestinal permability test? Any views on its accuracy?

Jenny

Yes twice....first time back when they were still Great Smokey Mountains lab years ago. Last time 2 years ago, ordered by Dr Peterson. I have done other testing with them as well. They have been at this a while and are very competent. Sorry, I have no reference with which to compare the accuracy of this particular test, but I know that it does measure level of severity, and not just pos/neg. To the best of my understanding, the method used is very simple and probably has a high accuracy rate, eliminating false readings. Maybe the lab would give you the stats on that? It may even be on their website.