Encapsulating leaky gut repair supplements in capsules to target the colon (where bacteria & LPS live) rather than the sterile small intestine

Hip

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Some theories hypothesize that LPS may be entering the blood from a leaky gut (intestinal hyperpermeability) and playing a causal role in diseases such as ME/CFS.

Now there are two main types of leaky gut: a leaky small intestine, and a leaky colon.

Since the small intestine is more or less sterile, and contains no bacteria (except if you have SIBO), presumably a leaky small intestine will not normally cause any LPS to translocate into your bloodstream.

Presumably it is only if your colon is leaky that you may get LPS entering into the blood circulation, because normally all your gut bacteria are confined to the colon.



If we assume translocated LPS is playing a role in ME/CFS, and want to try some leaky gut repair supplements like glutamine to treat leaky colon, then we would need to encapsulate these supplements in capsules that will only release their contents once they reach the colon.

Ordinarily, if you take leaky gut repair supplements like glutamine, they will enter the small intestine and help treat any leakiness present there; but glutamine will get digested along the 20 foot length of the small intestine, and I don't think any will reach the colon.

So I think normally, leaky gut supplements may only help repair the small intestine, but may not repair the colon.

But it's colon leakiness that would seem important to target, as that's where all the bacteria and LPS is found in your digestive system.

If we can treat colon leakiness, then perhaps this will ameliorate ME/CFS symptoms. Especially in ME/CFS patients with gut dysbiosis (where the populations of harmful bacteria or fungi in the colon outweigh the populations of beneficial bacteria).



So I started looking around for capsules that could deliver their contents to the colon. This is not the same as enteric capsules, which are designed to resist stomach acid and deliver their contents to the small intestines. We want colonic delivery capsules.

And indeed, I found such colonic capsule technology does exist. A company called Eudragit make a special capsule coating that is designed resist the stomach and small intestine environments, and only degrade and release the capsule contents once the capsule reaches the colon. It's the Eudragit S 100 product (which you can buy for $26) which ensures that capsules remain intact until they reach the colon.

However, I have not yet found any info on how to use Eudragit S 100. I think it is a chemical compound which you paint on to (or possibly melt on to) capsules to provide a protective layer that only degrades once the capsule reaches the colon.

So with Eudragit S 100, I may be able to convert some ordinary glutamine capsules into colonic capsules. But at the moment I need to find an instruction manual for Eudragit S 100. This is not a consumer product, so the info on how to use it is hard to come by.



So this is one my projects: to use Eudragit S 100 or some similar system to create colon delivery capsules containing glutamine and other leaky gut supplements, which I hope might reduce any colon leakiness and LPS leakage, and in turn improve ME/CFS symptoms.

(If anyone can come up with other ideas on getting leaky gut supplements into the colon, please post).

I listed some supplements and drugs which help reduce leaky gut here, so if these can be placed into colon delivery capsules, they can then target the colon. Glutamine is considered the most effective leaky gut fixer, but there are many other supplements that have been demonstrated in studies to reduce leaky gut.

By the way, if you want to get tested for leaky gut, note that the lactulose/mannitol leaky gut test only checks the small intestine; it cannot detect any colon leakiness you may have. The polyethylene glycol (PEG) test checks your intestines as a whole for leakiness (the small intestine and the colon). The sucralose test specifically checks just the colon for leakiness (but I am not sure if this test is commercially available). Ref: 1



There are two ways I am aware of that translocated LPS may affect the immune system and thereby play a role in ME/CFS and other diseases:

(1) Translocated LPS may cause immune priming: this is the phenomenon in which an initial exposure to an inflammatory factor such as LPS or interferon gamma makes immune cells far more sensitive to reacting to any further exposures. So later exposures to other inflammatory factors create much stronger inflammatory responses from these cells.

So for example if you have leaky colon (often found in IBS-D), the translocated LPS may sensitize immune cells. Then if you later catch a virus which induces interferon gamma, that may create too strong an immune response. See here, here and here for info on immune priming.

(2) Translocated LPS may cause endotoxin tolerance: this is where the body's inflammatory response to LPS becomes diminished with repeated exposure to LPS (in some ways endotoxin tolerance is the diametric opposite to immune priming). Michael Maes et al in a recent paper suggested ME/CFS might involve endotoxin tolerance
 
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Hip

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@Hip - thanks for all the info, it's very interesting! But what is LPS?
LPS is lipopolysaccharide, an endotoxin found in the cell walls of Gram-negative bacteria. It is a highly pro-inflammatory substance. When you take antibiotics which kill bacteria, it is the LPS from these killed bacteria which causes the Herxheimer reaction.
 

Hip

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Isn’t that what vsl3 is supposed to do? Why is used for Colitis
All regular probiotics are destined for the colon.

Probiotics are sometimes supplied in enteric capsules, so that the friendly bacteria they contain is not destroyed by the stomach acid. Once they are past the stomach, I believe it's all plain sailing for these friendly bacteria. I don't think the probiotic friendly bacteria are harmed in the small intestine.

I have not seen any probiotics that come in colonic delivery capsules.
 
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Thinktank

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Another way to help heal the leaky colon is to consume a 100% elemental diet for 3 weeks.
* Bring down bacterial load in colon - less LPS to leak through
* Reduce inflammation directly - no faeces / allergens / toxins etc. to irritate the gut wall.

That, in combination with Hip's idea of delivering certain enteric coated compounds to the colon may bring huge relief in LPS-induced inflammation.
I would add proven anti-inflammatories like boswellia serrata in medium to high doses.

I do believe though that diet needs to be adjusted.
 

S-VV

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Thanks Hip. I too found the Mae's paper very interesting. It promted me to start "anti-lps" therapy, consisting of cholestyeramine, activated charcoal, bentonite clay, zeolite and lactoferrin, all of which can bind to endotoxin.

I would also use sevelamer, if it were not so expensive.

You may also be interested in enteric phosphatidyl choline, which is used for ulcerative colitis.
 

S-VV

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For leaky gut, I use colostrum (30g/d) and glutamine, though without any coating. I am a bit apprehensive about glutamine both because of its high amino group content and it's possible conversion to glutamate.

After all glutamine= glutamate + amine.

High ammonia levels have been implicated in unrefreshing sleep and sleep phase shift.
 

Hip

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For leaky gut, I use colostrum (30g/d) and glutamine, though without any coating. I am a bit apprehensive about glutamine both because of its high amino group content and it's possible conversion to glutamate.
I tried taking a cocktail of leaky gut supplements for around 6 months (the supplements I listed in this post), but did not notice much.

I have not been tested for leaky gut (but I do have IBS-D, and 39% of those with diarrhea predominant IBS were found to have leaky gut).

But it occurred to me recently that leaky gut of the colon may be the issue we should be targeting, rather than leaky small intestine, and I don't think any of these standard leaky gut supplements will reach the colon when taken orally, as they will be digested in the small intestine.



um ... insertion?
If you administer leaky gut supplements as suppositories, they may have an effect in the rectum, but it is doubtful they would travel against the flow of digestion, and reach the far end of the colon. An enema with glutamine (which is considered the most effective leaky gut supplement) might stand a better chance of reaching the full length of the colon. Though given that leaky gut takes a long time to heal (many months), administering daily enemas would be a chore.



@Hip You found out how to use that Eudragit yet?
I've not looked into it recently, but it's on the agenda.

In the Eudragit manufacturer's catalog, they talk about "hot-melt extrusion & spray drying" of Eudragit polymers, so I am guessing that Eudragit is a plastic polymer compound that you coat capsules with.

The application of Eudragit to a capsule might thus involve an industrial process beyond the reach of the person working at home in his kitchen.

Ideally you would want to buy ready-made empty 000-size capsules pre-coated in Eudragit that you could just fill with the supplements of you choice, but I have not been able to find any such capsules.


There are different formulations of Eudragit, and each formulation is designed to disintegrate at certain pH levels. Different parts of the digestive tract have their own characteristic pH, so that's how they can make capsule coatings which open at specific points along the digestive tract.

Eudragit S 100 is designed to disintegrate in the colon at pH 7, Eudragit L 100 disintegrates in the jejunum at pH 6 to 7, and Eudragit L 100-55 disintegrates in the duodenum at pH 5.5.

The catalogue also mentions an easier-to-use PlasACRYL product.
 
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SYMPROVE is guaranteed to reach the large intestine and it has been proved by the Kings College in London. It contains water,extract of germinated barley. Live activated cultures of. L rhaamnosus, E faecium, L planturum, L acidophilus, vitamin c, acidity regulator, plus preservatives. ( too tired to write them all down)
Diet is really important too.:hug:
 

Hip

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SYMPROVE is guaranteed to reach the large intestine
Most probiotics will reach the colon to some extent (otherwise they would not be of much use).

However, it's not clear what fraction of a leaky gut repair supplement like glutamine will reach the colon, as a lot I think will be absorbed in the small intestine.
 

Rufous McKinney

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which I hope might reduce any colon leakiness and LPS leakage, and in turn improve ME/CFS symptoms.
Sounds like a good experiment.

Sharing: I used to take enteric coated colostrum. Very expensive pills. Then: there it is in the toilet, not dissolved at all. Ceased buying those.

This makes me wish to suggest: enema? Isn't that a direct route to the Zone of Interest?

I'm continuing my four chinese Traditional Herbs for IBS-d and gut is Very Improved. Not taking any probiotics at the moment.
 

Rufous McKinney

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Most probiotics will reach the colon to some extent
I see enema was already suggested.

My husband indicated he'd heard that they can be absorbed thru the bloodstream via the mouth. I think this is also a viable route for probiotics at least.

I previously purchased some probiotics designed for oral health....dont' have them any more. I'm going to check if the Japanese have looked into this. (they design good probiotics)