Mechanisms Behind The Leaky Gut

[mle_ii]

Haven't seen this here yet, so I thought I'd post this. I was doing some research on zonulin and came across this document:
http://www.autismone.org/uploads/Owens%20Susan.doc

Haven't examined all the science/research, but a quick look at a few parts of the science look very sound.

Ok, I've been reading a lot more about zonulin and what I've read thus far is pretty darn amazing.

Of course we all know by now that Zonulin causes these tight junctions, the barrier from the contents of the GI to the other side of the cells, to open.

It appears that in folks with celiac disease and even treated celiac disease folks that the tjs are open a lot more than normal folks. And that when exposed to gliadin that zonulin causes these tjs to open even more, a lot more in celiac disease and celiac disease-treated, but also (news to me) in folks without celiac disease. It also appears that bacteria that reside in the gut also opens these tjs (even newer news to me).

http://gut.bmjjournals.com/cgi/content/full/48/4/503

BACKGROUND AND AIMSAltered intestinal permeability is a key pathogenetic factor of idiopathic bowel inflammation. We investigated in the rat if changes in the composition of the bowel flora can alter colonic permeability.
METHODSA colonic segment was surgically excluded from faecal transit and brought out as a loop to the abdominal wall through two colostomies. The loop was used for colonisation with specific bacterial strains after eradication of the native flora with antibiotics. Lumen to blood clearance of dextran (molecular weight 70 000) and mannitol (molecular weight 182) was measured in rats recolonised with a single bacterial strain from rat colonic origin, and in control rats whose colonic loop was kept free of bacteria by antibiotics. Actual colonisation was confirmed by culture of segment effluents.
RESULTSColonisation with Escherichia coli, Klebsiella pneumoniae, and Streptococcus viridans significantly increased lumen to blood clearance of mannitol. Colonisation with Lactobacillus brevis had the opposite effect and reduced permeability to mannitol. Bacteroides fragilis did not induce significant changes. Permeability to dextran was not altered by any of the strains tested.
CONCLUSIONSCertain commensal bacteria can modify colonic wall permeability to luminal substances.

Didn't realize that even bacteria had the key to our bodies.

Here's this one that shows that zonulin was part of the key for the bacteria.
http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12404235

Once the tjs are open more than normal this allows stuff to pass through, in some cases gliadin and in others other food proteins or even bacteria. Once they pass through we develop the antibodies to these pathogens and all heck breaks loose.

Now I'm wondering why the gut would allow this bacteria to do this. Perhaps gliadin looks to what ever is turning on the zonulin like the bacteria and thus lets stuff on in.

Mike

[Polly]

Hi Mike,

Thanks for those interesting tidbits. Have you seen the bottom article in the "Current Reserach" forum? It is a summary of Dr. Fasano's research on zonulin.

I think you are correct with your last statement. Gliadin and bacteria may be similar in stucture, or at least part of their structures are similar.

Love,

Polly

[tex]

Mike,

I found the first article you cited, (by Susan Owens), to be most interesting. It's well written, easy reading, and the discussions of the links with calcium and oxalates are veeeeeeeeerrrrrry interesting. That's very useful background information. Also of interest is the observation that paracellular transport can occur with other tissues, such as the bladder, kidneys, and the blood brain barrier. I think we've previously discussed the possibility of a "leaky" blood brain barrier, but I don't recall any discussion about leaky barriers in the bladder or kidneys, (to say nothing of the liver or other organs).

The discussion of how fat malabsorption causes calcium to become unavailable to trigger the closing of the tight junctions, and put a stop to the paracellular transfer, certainly helps to illuminate what occurs in our own gut during an active episode.

Consider this quote:

We have found that some of the children who previously had horrible reactions to rice and corn and even wheat and dairy are tolerating some of these foods and other starches when sticking to a lower oxalate diet. The increased tolerance to these foods may have come from getting the tight junctions closed which would eliminate the overexposure of the immune system to these food antigens. If this is truly the case, the change might diminish allergic reactions to food and might possibly help restore the disaccharidase activity.

This certainly applies to some of us, especially those who can now eat certain foods that we couldn't tolerate before we healed. Maybe we need to learn more about oxalates, and high oxalyte foods. Maybe others among us could eat certain other foods, if they avoided high oxalate foods.

Here's a site with oxalate ratings, and diet suggestions. Note that cocoa, chocolate, and many of the items that some MIs are having problems with, are in the high oxalate catagory. (Jean, are you reading this?) I had problems with many of these high oxalate foods before my gut healed, and I still have probems with some of them, if I eat very much of them.

http://www.branwen.com/rowan/oxalate.htm

Tex

[starfire]

Very interesting..........Thanks for the link, Tex.

Love, Shirley

[cludwig]

Hi Friends,

So, If I am reading this article correctly (big if), does it confirm what some have found ..that taking calcium supplements with meals controls their loose stools? I just remember Marsha and maybe Andrew saying that the calcium supplements helped. It sounds like the article suggests that calcium is used to get rid of the oxalates and helps close the gates. Is that what you guys got too?

Love, Cristi

[tex]

Hi Cristi,

Though it might infer it, if the article mentioned that calcium supplements might attenuate diarrhea, I missed that part. (That doesn't mean that it won't help, it just means that I didn't notice it in the article). What it does say is that untreated celiacs have a real problem, since the calcium in their lumen is likely to be unavailable, because it will be tied up with fat, (which will not be absorbed), and on the other side of the gate, their calcium serum levels are likely to remain low, due to this chronic malabsorption problem.

If there is any calcium in the lumen that escapes the fat, then any oxalates will tend to tie it up, also. Therefore, insufficient calcium is available to trigger the gate closing mechanism.

Apparently this action is completely independent from the influence of zonulin, which means that either mechanism can cause the junctions to remain open, regardless of the state of the other process. IOW, either inadequate levels of calcium, or excess levels of zonulin, (or both), can cause the junctions to remain open.

I agree with you, though - it is tempting to think that calcium supplements might help, provided that fat and oxalate intakes are limited, and provided that zonulin levels are suppressed by the absence of gluten in the diet. If calcium supplementation helped, though, one would think that celiacs would have discovered that possibility by now, since CD has been around for quite some time.

Of course, maybe celiacs as a group, are more prone to trust their doctors, so they aren't as inquisitive, and as prone to experiment, as MCers. LOL.

Love,
Tex

[cludwig]

Hi Tex,

Thanks for clearing that up for me. After the second page it all starts sounding the same. It is true that choosing foods from the SCD that are allowable, I've naturally gone for the high oxalate foods. Who ever thought diet could get so complicated.

Love,
Cristi

[tex]

Hi Cristi,

You're so right! For something so simple, it can also be ridiculously complicated. It seems that for almost every type of food we can think of, somewhere, someone has written an article describing why it is bad for us.

And, for every type of food that we cannot eat, because we know it is unhealthy, or we have an intolerance for it, someone is promoting that food item as an ideal addition to a healthy diet. It's hard to win, and it's confusing. There are way too many angles to be considered.

Love,
Tex

[Polly]

How true, Tex. SIGH.

Maybe someday we can have a DNA test that tells each of us exactly the best foods to eat or avoid, given our genes.

I see that the foods highest in oxalates are also the foods highest in calcium for the most part. And, I've heard for years that the Caltrate that comes in the purple box somehow helps control the D - they even advertise on the box now that it is healthy for the colon. But this is not necessarily true for other calcium supplements. I'm not sure anyone really knows why the Caltrate works.

One of these days, hopefully, we'll be able to fit all of the pieces together.

Love,

Polly

[bobh]

Interesting stuff you folks found on "Leaky Gut" (see synonym study under "Bob H").

Hi Cristi, ...If there is any calcium in the lumen that escapes the fat, then any oxalates will tend to tie it up, also. Therefore, insufficient calcium is available to trigger the gate closing mechanism.

...IOW, either inadequate levels of calcium, or excess levels of zonulin, (or both), can cause the junctions to remain open.

...I agree with you, though - it is tempting to think that calcium supplements might help, provided that fat and oxalate intakes are limited, and provided that zonulin levels are suppressed by the absence of gluten in the diet.

Do any of you folks have an opinion on some of the powdered instant "Cal-Mag" drinks? There are several brands at Health Food stores, sometimes I take one made by Nutrina (pour hot water on a teaspoon of this white powder). My wife takes it every night to help sleep, I hadn't noticed much benefit but only take it occasionally.