Zonulin, intestinal permeability and MS

[dignan]

interesting research that could have MS implications....

Discovery could lead to the prevention, and possibly treatment of autoimmune diseases such as Type 1 diabetes

February 23, 2005 - Scientists at the University of Maryland School of Medicine in Baltimore have identified a way to prevent Type I diabetes in rats that are genetically prone to develop the disease.

The discovery could one day lead to the prevention, and possibly to the treatment, of autoimmune diseases such as Type 1 diabetes, which affects more than one million people in the United States. The findings are published in the February 22, 2005 edition of the Proceedings of the National Academy of Sciences.

In the study led by Alessio Fasano, M.D., professor of pediatrics, medicine and physiology and director of the University of Maryland Mucosal Biology Research Center, researchers used an animal model of diabetes and found a way to prevent the disease by changing the permeability of the intestinal wall.

Earlier research by Dr. Fasano and colleagues led to the discovery of the human protein zonulin. They observed that zonulin regulates the permeability of the intestines by controlling the opening and closing of specialized structures that act like gates between cells. When the body produces too much zonulin, these gates get stuck open for too long and allow undigested foodstuff, toxins and other bacterial and viral particles access to the immune system. That contact, in turn, leads to the production of antibodies that can destroy the insulin-producing islet cells in the pancreas among people genetically predisposed to develop Type 1 diabetes. The final result is the appearance of Type 1, or insulin-dependent, diabetes.

Dr. Fasano’s group also discovered that zonulin is produced in very large amounts in people who have autoimmune disorders such as diabetes, celiac disease, multiple sclerosis and rheumatoid arthritis. The researchers performed their latest study on rats that were genetically prone to develop Type 1 diabetes.

“With autoimmune diseases, the body mistakes its own tissues as foreign, resulting in an attack and destruction by the body’s own immune system. These diseases are all characterized by an extremely permeable intestinal wall,” says Dr. Fasano. “We already knew that there was a distinct connection between an increase in zonulin levels and an increased permeability of the intestines. With this study, we’ve been able to identify a way to prevent zonulin from causing leakage from the intestines as it does in people with these autoimmune diseases.”

With funding from the National Institutes of Health, Dr. Fasano and his research team used diabetes-prone rats to test the effectiveness of a zonulin inhibitor peptide called AT-1001, which is known to prevent zonulin from regulating intestinal permeability. The peptide prevented the development of diabetes in the vast majority of the animals tested. Only 27 percent of those that were given water containing AT-1001 developed diabetes. “In essence, we saw that this peptide stopped the sequence of events that leads to diabetes,” Dr. Fasano says.

Dr. Fasano adds that this significant discovery could eventually lead to the development of an oral medication to arrest autoimmune diseases in the early stages. Immediate plans call for clinical trials to test the use of AT-1001 in patients with celiac disease. Alba Therapeutics, a Baltimore-based biopharmaceutical company, has already sought approval from the FDA to conduct those trials.

http://www.news-medical.net/?id=7937

[HappyDaddy]

Thank you very much for this post.

I find it very interesting since I have just been diagnosed with "leaky gut syndrome", which seems to be the root-cause of all my problems, including MS.

Best wishes.

[Brian]

If this proves out, then is MS an infectious disease vs. being an autoimmune disease?

[feesher]

see this link:
http://www.llpoh.org/archives/00000111.html

Earlier research conducted by Dr. Fasano discovered that zonulin is also involved in the regulation of the impenetrable barrier between the blood stream and the brain, known as the blood-brain barrier.

[Outlawbiker]

This article gives me an incredible amount of hope that I might be able to protect my children from developing MS or any other of the Autoimmune diseases that I (and now them) may be genetically predispositioned to be susceptable to.

They need to hurry up and put a pill out that can be taken like Prevacid and everything will be hunky-Dory!!!!

[noddlebean]

Would using Anti-oxidents help do you think?

If the toxins are getting into the immune system and or blood supply from the intestine then keeping these under control within the body should help keep the immune in check.

I am taking anti-oxidents of the following:

N-Acetylcysteine (NAC)
Q10 Enzyme. This I take for the effects of Lipitor but is also known as a good Anti-oxident.
Grape Seed Extract - another good one.

All these are available over the counter.

This is how I take reading this article.....

Antioxidents are excellent for the body anyway. Varous foods supplying some antioxident properties.

Jill

[cervocuit]

A research by Fasano’s team in 2011 :
http://physrev.physiology.org/content/91/1/151.long

I found the following graphic from this paper very hopefull especially for SPMS. Because who knows what will happen if we could lowering the level of Zonulin in SPMS, when it’s the level of healthy controls and RRMS in remission.



Zonulin is a protein produced by the intestin in presence of gliadin (a piece of gluten) but mostly by some bacteria in the gut.
In fact, Fasano’s work on celiac showed that « celiacs produce 30 times as much zonulin as non-celiacs, even though the non-celiacs were not eating gluten-free diets while the celiacs had been off gluten for over two years! »

This suggests that something besides gluten may be causing zonulin production in celiacs.
http://blog.cholesterol-and-health.com/ ... in-is.html

this guy made this graphic from this paper
http://www.google.fr/url?sa=t&rct=j&q=& ... 3194,d.ZWU

bacteria in the gut and often called the gut microbiome and I guess we can hope a lot from the tremendous amount of ongoing research on this field.

In the meantime : Diet, stress managment, sun, exercice …

[cheerleader]

Thanks for digging up dignan's thread on Fasano and his zonulin discovery, cervocuit. We've had similar discussions on the CCSVI thread. Zonulin is a known endothelial dysrupter and it opens up tight junctions between endothelial cells. It shows up in other places, aside from the gut--
Zonulin is implicated in acute lung injury
http://www.ncbi.nlm.nih.gov/pubmed/23564505
it is higher in sepsis patients
http://www.biochemia-medica.com/2013/23/107

Probiotics have been shown to reduce zonulin levels in plasma-
http://link.springer.com/article/10.118 ... -2783-9-45

Agree--eating whole foods, taking probiotics, exercise, endothelial healthy living can be helpful.
cheer

[Leonard]

I think the cause for it all, incuding the leaky gut and the raised zonulin in gut and in vessel walls, lies here: http://www.mold-survivor.com/cfs2.html

I think this Brussels based professor in the video below makes the right assessment: the bowel problems are often seen in conjunction with an abnormal gut flora. Most likely this is caused by changes in the immune system. A chronic low-level inflammation changes acidity and other things. I am sure Zonulin is part of the picture. (unfortunately in Dutch)

Many other things he says are of interest to us such as CFS is caused by chronic low level inflammation. You could almost replace ME/CFS with MS. For MS, I am sure, is also caused by a chronic low level infammation (Herpes/VZV/EBV). For more details, see the last few pages of
http://www.thisisms.com/forum/general-d ... 15188.html

[Kronk]

Interesting that some researchers attribute the beneficial effects of testosterone to its effect on gut flora. Others say the gut flora is responsible for a rise in testosterone, either way there is a clear link.

http://www.technologyreview.com/news/50 ... -diabetes/
"...Transplanted Gut Bugs Protect Mice from Diabetes..."

This could explain the benefits of Fecal Microbial Transplant as well.

[jimmylegs]

zinc intake and status affects testosterone levels, the composition of the gut flora, and intestinal permeability

Zinc status and serum testosterone levels of healthy adults
http://www.ncbi.nlm.nih.gov/pubmed/8875519

Zinc deficiency is prevalent throughout the world, including the USA.
Severe and moderate deficiency of zinc is associated with hypogonadism in men.
However, the effect of marginal zinc defficiency on serum testosterone concentration is not known.
We studied the relationship between cellular zinc concentrations and serum testosterone cross-sectionally in 40 normal men, 20 to 80 y of age.
...
Serum testosterone concentrations were significantly correlated with cellular zinc concentrations in the cross-sectional study...
Dietary zinc restriction in normal young men was associated with a significant decrease in serum testosterone concentrations after 20 weeks of zinc restriction...
Zinc supplementation of marginally zinc-deficient normal elderly men for six months resulted in an increase in serum testosterone from 8.3 ± 6.3 to 16.0 ± 4.4 nmol/p (p = 0.02).
We conclude that zinc may play an important role in modulating serum testosterone levels in normal men.

pig studies, but still interesting:

The impact of high dietary zinc oxide on the development of the intestinal microbiota in weaned piglets
http://www.ncbi.nlm.nih.gov/pubmed/24118028

This study has shown that the application of dietary zinc at high concentrations leads to transient and lasting effects during the development of the intestinal microbiota, affecting composition as well as metabolic activity.

from http://www.thisisms.com/forum/general-d ... ml#p211406 :

Increased dietary zinc oxide changes the bacterial core and enterobacterial composition in the ileum of piglets
http://animalsci.highwire.org/content/89/8/2430.short

Increased dietary ZnO led to an increase of less prominent species and, thus, had a major impact on the bacterial composition and diversity in piglets. This effect may help to stabilize the intestinal microbiota in the sensitive postweaning period

from http://www.thisisms.com/forum/general-d ... ml#p197279 :

Zinc supplementation tightens “Leaky Gut” in Crohn's disease
http://onlinelibrary.wiley.com/doi/10.1 ... 00003/full

related discussion on zinc and leaky gut

http://www.thisisms.com/forum/chronic-c ... ml#p174244

http://www.thisisms.com/forum/general-d ... tml#p54065

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