A gluten protein normally is too big in order to pass the intestinal barrier!

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Everywhere we hear about how bad gluten or wheat are because they cause leaky gut and are highly immune-reactive.

Guess what, as I understood this study, gluten is not the culprit, zonulin is. They found increased levels of zonulin in patients with celiac disease. These levels lead to a leaky gut and this is the only reason why gluten can pass the intestine barrier and cross into the bloodstream where it is attacked by antibodies.

In a healthy(!) person the zonulin levels are normal and big proteins like gluten CANNOT pass the intestinal barrier. These people CAN eat gluten and will not have any problems!

But how can gluten pass? This was what Prof Fassano asked himself. How can gluten pass the barrier if it normally is much too big. The answer: Zonulin opens the barrier so now even big proeins like gluten get through and get into contact with blood.

"People with celiac have an increased
level of zonulin, which opens the junctions between the cells. In
essence, the gateways are stuck open, allowing gluten and other
allergens to pass. Once these allergens get into the immune system,
they are attacked by the antibodies," adds Dr. Fasano.
Next to antivirals, zonulininhibitors seem to be my biggest hope regarding treatment of CFS.

Full abstract:

1. Originally Released: May 1, 2000
Contact: Ellen Beth Levitt, eblev...@umm.edu, 410-328-8919
RESEARCHERS FIND INCREASED ZONULIN LEVELS AMONG CELIAC DISEASE
PATIENTS
Researchers at the University of Maryland School of Medicine have
found that the human protein zonulin, which regulates the permeability
of the intestine, is at increased levels during the acute phase of
celiac disease. The discovery suggests that increased levels of
zonulin are a contributing factor to the development of celiac disease
and other autoimmune disorders such as insulin dependent diabetes,
multiple sclerosis, and rheumatoid arthritis. The findings are
published in the April 29 issue of the journal Lancet.
"Zonulin works like the traffic conductor or the gatekeeper of our
body's tissues," says lead author Alessio Fasano, M.D., professor of
pediatrics and physiology at the University of Maryland School of
Medicine, and director of Pediatric Gastroenterology and Nutrition at
the University of Maryland Hospital for Children. "Our largest gateway
is the intestine with its billions of cells. Zonulin opens the spaces
between cells allowing some substances to pass through while keeping
harmful bacteria and toxins out," explains Dr. Fasano.
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.
Celiac disease offered Dr. Fasano and his team a unique model for
understanding the dynamic interaction between zonulin and the immune
system. Celiac disease is a genetic disorder that affects one out of
every 300 people in Europe, but its prevalence in the United States is
not fully known. People who suffer from the disorder are unable to eat
foods that contain the protein gluten, which is found in wheat and
other grains. The gluten sets off a reaction that can cause diarrhea,
abdominal pain, malabsorption of nutrients, and other gastrointestinal
problems. Celiac disease can be easily treated by avoiding foods with
gluten.
With celiac disease, the body reacts to gluten by creating antibodies
that attack the intestine and cause severe damage over time. Unlike
other autoimmune disorders, scientists also know that celiac disease
is triggered by a specific antigen, which is the protein gluten.
Celiac disease is also known to cause increased permeability of the
intestine. In addition, many people who suffer from celiac disease
also suffer from other autoimmune disorders.
The research team examined the intestinal tissue of seven people with
celiac disease, and six patients without the disease. Patients with
active celiac disease showed higher levels of zonulin and anti-zonulin
antibodies compared to non-celiac patients and patients in remission,
who were eating a gluten-free diet.
"With celiac disease, we could never understand how a big protein like
gluten was getting through to the immune system. Now we have the
answer," explains Dr. Fasano. "People with celiac have an increased
level of zonulin, which opens the junctions between the cells. In
essence, the gateways are stuck open, allowing gluten and other
allergens to pass. Once these allergens get into the immune system,
they are attacked by the antibodies," adds Dr. Fasano.
"I believe that zonulin plays a critical role in the modulation of our
immune system. For some reason, the zonulin levels go out of whack,
and that leads to autoimmune disease," explains Fasano.
Dr. Fasano adds that more research is needed. He is currently
conducting experiments with diabetic rats. Preliminary results from
his experiments show that insulin dependent diabetes occurs in lab
rats about three to four weeks after increased intestinal
permeability. The researchers believe the increased intestinal
permeability is associated with increased levels of zonulin.
"We are at the threshold of exciting discoveries in this field," says
Dr. Fasano. "We now have a new way of looking at our cells. Our cells
are not stacked together like bricks. They are a dynamic field, which
is constantly in flux."
 
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dannybex

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Yes...very interesting...

Very interesting Diesel -- you're certainly working hard trying to sort this all out. I too had never heard of zonulin, or it's affects on the gut.

I've mentioned VSL#3, the pricey probiotic, in other posts. It was shown to digest gliaden when added to wheat dough. I just googled 'zonulin', which brought me back to the same story...

"This study confirmed proteins extracted from dough pre-treated with VSL#3 released less zonulin, the protein that controls tight junctions between intestinal lining cells. Zonulin is believed to be important in the development of celiac disease. It increases permeability of leaky gut that predisposes to celiac and non-celiac gluten toxicity. Less F-actin reorganization within the cells also was noted. F-actin controls intestinal permeability."

http://thefooddoc.blogspot.com/2007/02/probiotic-vsl3-breaks-down-toxic.html

So...perhaps (just a guess here) one of the reasons that gluten intolerance develops is because of microbial imbalances -- not enough 'good' probiotic bacteria, or not enough of certain strains of bacteria.:confused:

There's more discussion of zonulin and other possible factors, like oxalates, on this celiac page:

http://www.celiac.com/gluten-free/topic/47795-zonulin-leaky-gut-and-gluten-sensitivity/

Thanks Diesel,

d.
 

dannybex

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Enzymes for gluten / casein intolerance...?

Have any of you tried digestive enzymes designed to break down gluten (and/or casein) like Petizyde or this new one called GlutenEase? Peptizyde seems to work okay (I tried it a couple years ago) but the latter seems to be getting some glowing reviews, with some cautions:

http://www.enzymestuff.com/basicsproductguidelines.htm

"GlutenEase (Enzymedica) - very effective product targeting both protein and carbohydrate portions of gluten and casein. Effective enough to replace GFCF diet for many people. Not intended for celiacs to leave gluten-free diet, but acts as 'safety net' for accidental exposures. Lessens symptoms for many with celiac. Does not cause adverse reactions some other gluten-targeting enzyme products do in celiac."

(the site was started by a woman with autistic kids, she doesn't sell the products)

I also tried "No-Fenol", which greatly helps digest phenolic/high salicylate foods, again 2+ years ago, off and on probably going back about 5 years, and it seemed in hindsight to help a great deal. Was definitely doing a lot better than I am now, and again in hindsight, have been inadvertantly eating a lot of foods during the past 9 months or so that are very high in sals/phenols.

Anyway, just wanted to add these possibilities to the mix. Apparently some folks can use them for a few months, then (I suppose as the gut heals?) they require less, and some are even able to stop taking them. Just wish all this stuff wasn't so pricey -- especially that VSL3.

That's a shame that you don't have access to it Diesel. Sorry, I've forgotten...are you in the UK? Was it actually covered by your health care provider?

d.
 
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Dannybex,

that's funny, I just watched the 68 minute video from Prof Fasano about leaky gut and autism. He spoke about gluten, the human body does not have any enzymes that break down gluten. You can put gluten into a glas filled with gastric acid and all other juices and bacteria in our body. 8 hours later the gluten will still be there. Put your finger into the glas and within 30 seconds it will be reduced tothe bone. I didn't know that there were enzymes you can use but I cannot imagine that they break down all the gluten.

The next thing that was very disappointing for me, a gluten/casein free diet based on studies and expectations should only help about 20% of autistic children, not more.
Gluten increases zonulin production by the way. I didn't understand the difference between a healthy person and an ill. The healthy person produces less zonulin of course but his immune system also attacks the gluten in another/correct way.

They stopped selling the VSL#3 here in Germany.

What I missed in the video where answers about the following questions:

What reduces zonulin?
Why does eating gluten lead to problems in some people? Do they have a certain gene for that?
Is eating gluten problematic even if you are healthy?

n8
 
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Diesel,

Don't forget that Fasano is new to the autism world. He has a lot to learn there. I would NOT rely on these gluten studies on autistic children. Very limited studies on a very limited number of children, and of course flawed. And all the political crap. I don't know where he got this 20% figure but as far as I am concerned, it is crap.

Karin
 
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Diesel,

Don't forget that Fasano is new to the autism world. He has a lot to learn there. I would NOT rely on these gluten studies on autistic children. Very limited studies on a very limited number of children, and of course flawed. And all the political crap. I don't know where he got this 20% figure but as far as I am concerned, it is crap.

Karin
Yes, the studies are not very reliable. Do you think the number is higher? Fir me it looks that many mothers put their autistic children on a gluten/casein free diet but I do not know if it helps their children. Some insight from someone of the autistic community would be nice.
 
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Deisel,
The Autism Research Institute surveys parents about biomedical interventions, and the last survey suggested 66% of approx 2500 children improved on a gluten free/casein free diet. Gluten free on its own doesn't seem to have been surveyed.*

(I know several people gluten free or gluten and casein free and the quality of their diet varies a lot, so there are other variables.)

I was wheat free, then gluten and dairy free, nowdays all grain free (still avoiding dairy), and I've noticed improvements at every step.

:) Anne.

* Link to study (see bottom half of the page for the ARI 2008 study

http://www.gfcfdiet.com/dietsurveysept2.htm
 

Frank

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gluten-free can also mean you avoid other things found in bread, beer and spaghetti. I'm thinking of fungal byproducts. As i understand the zonulin is also a byproduct of a micro-organism?
 

Athene

ihateticks.me
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Diesel thank you for starting this fascinating thread, and thank you everyone else for the other really useful info.

I just read that zonulin is expressed by the cholera pathogen, which would explain why I developed extremely leaky gut after having cholera. I already had gluten allergy but it all became far worse. I asked so many doctors what are the long term effects of cholera on the intestine and they all went blank. I told them it had damaged my intestine in a permanent way and I wanted to understand how, as I was sure that was the key to improving the situation. They all took the attitude that I should be grateful I was alive, and leave it at that.

It's REALLY nice to have an answer at long last.
 
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Deisel,
The Autism Research Institute surveys parents about biomedical interventions, and the last survey suggested 66% of approx 2500 children improved on a gluten free/casein free diet. Gluten free on its own doesn't seem to have been surveyed.*

(I know several people gluten free or gluten and casein free and the quality of their diet varies a lot, so there are other variables.)

I was wheat free, then gluten and dairy free, nowdays all grain free (still avoiding dairy), and I've noticed improvements at every step.

:) Anne.

* Link to study (see bottom half of the page for the ARI 2008 study

http://www.gfcfdiet.com/dietsurveysept2.htm
Thanks, that's what I was going to post. 2/3 of good response seems right to me.
 

xrayspex

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mutaflor from germany and now canada I think, research that gut supplement, hands down best one I have ever taken, can tolerate a lot more foods after 3 months of that and seem less sensitive in other ways too, I still avoid wheat but have been purposely occasionally trying a little for first time in like 8 yrs and nothing bad happens like in the past....but am not going to tempt fate too much
 

cigana

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Hi Diesel,

Thanks for posting this. I will try to answer your questions best I can just to give some input:

Why does eating gluten lead to problems in some people?

I think he was saying it is only a problem if the barrier is opened and that this mainly occurs as a result of dysbiosis. So only people with dysbiosis will have a problem.

Do they have a certain gene for that?

Only in the sense that the microbiome can be considered an extended genome.

Is eating gluten problematic even if you are healthy?

He said it wasn't a problem for healthy people.

The way I see it is even if gluten itself isn't enough on it's own to open the barrier if you are healthy, we should still not consume gluten (even if we are not gluten sensitive) because gluten only causes more zonulin to be released. Since PWC's have dysbiosis causing zonulin release, we don't want to add in gluten that will only lead to further zonulin.

I think he was implying (though he didn't say explicitly) that dysbiosis is the cause for celiac in the sense that dysbiosis is the major cause of the barrier opening and then the gluten can get to the bloodstream and provoke an immune response.

I have attached the Scientific American article he wrote on this.

Cig
 

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