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 quasi-sterile, and containing very little bacteria (except if you have SIBO), presumably a leaky small intestine will not normally cause much 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.
In this paper, table 1 shows the colon has 10^11 bacteria per ml, whereas the upper small intestine has only 10^4 per ml, and the lower small intestine has 10^8 per ml. In SIBO you get up to 10^5 per ml, see this paper. So the colon has bacterial densities at least a 1000 times higher than the small intestine.
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
Now there are two main types of leaky gut: a leaky small intestine, and a leaky colon.
Since the small intestine is quasi-sterile, and containing very little bacteria (except if you have SIBO), presumably a leaky small intestine will not normally cause much 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.
In this paper, table 1 shows the colon has 10^11 bacteria per ml, whereas the upper small intestine has only 10^4 per ml, and the lower small intestine has 10^8 per ml. In SIBO you get up to 10^5 per ml, see this paper. So the colon has bacterial densities at least a 1000 times higher than the small intestine.
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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