Severe COVID-19 Is Fueled by Disrupted Gut Barrier Integrity

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This seems aligned with this other paper that has been published recently on MIS-C after Covid-19:

Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier
https://www.jci.org/articles/view/149633

And patients in this study responded really well to larazotide, a zonulin antagonist. Better than steroids or IVIG. I have no idea why this peptide is not being fast-tracked for use in Covid-19.
 

msf

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This seems aligned with this other paper that has been published recently on MIS-C after Covid-19:

Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier
https://www.jci.org/articles/view/149633

And patients in this study responded really well to larazotide, a zonulin antagonist. Better than steroids or IVIG. I have no idea why this peptide is not being fast-tracked for use in Covid-19.
Or being trialled for ME for that matter. I have been tested for zonulin and it was found to be very high after eating wheat, which I could have guessed from my symptoms.
 

antares4141

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Twiv reacently did a podcast:
TWIV 769 MIS-C and leaky gut

Jargon they use cause the podcast is geared towards academics, I didn't get a lot out of it.

I have a similar problem with the types of studies you linked to.

Not to mention hard on the brain.

Most the articles I read are posted by science journalist who are good at translating all the jargon into language I can understand.

I've long suspected leaky gut cause my symptoms are always the least manageable after meals. Mostly have to sleep after eating. Which is what you have to do when you have a fever or flue. But with the fever and flue your body eventually clears it and you are able to get on with your life. A perpetual leaky gut if this is what I have not so much.

It is confusing reading about leaky gut. This site says it's an "unrecognized medical condition" https://en.wikipedia.org/wiki/Leaky_gut_syndrome except for in certain cases where their is inflammation than it's not a "unrecognized medical condition". https://en.wikipedia.org/wiki/Intestinal_permeability Which leads me not to know what to think!
 
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msf

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Twiv reacently did a podcast:
TWIV 769 MIS-C and leaky gut

Jargon they use cause the podcast is geared towards academics, I didn't get a lot out of it.

I have a similar problem with the types of studies you linked to.

Not to mention hard on the brain.

Most the articles I read are posted by science journalist who are good at translating all the jargon into language I can understand.

I've long suspected leaky gut cause my symptoms are always the least manageable after meals. Mostly have to sleep after eating. Which is what you have to do when you have a fever or flue. But with the fever and flue your body eventually clears it and you are able to get on with your life. A perpetual leaky gut if this is what I have not so much.

I have long suspected this but all the reading I have done says leaky gut is a quack diagnosis, https://en.wikipedia.org/wiki/Leaky_gut_syndrome except for in certain cases where their is inflammation than it's not a quack diagnosis. https://en.wikipedia.org/wiki/Intestinal_permeability Which leads me not to know what to think!
I am lucky in that my brain fog is minimal, and I had a reasonably scientific background to begin with. However, not having brain fog does not mean that I will necessarily have the energy to go through piles of papers with a fine toothcomb. I basically concentrate on the explanations or problems relating to ME that I find most convincing a priori (which I generally find on PR), and then read through articles looking for results that either confirm or refute that explanation or problem. This is much less demanding than trying to understand every part of the paper including all the methodology and statistical analyses.

If the problem is confirmed in this way, I will try to find something that should theoretically be able to treat it, usually just by googling or pubmeding the problem and various possible treatments. I then focus on the relevant results in the same way. I will then check to see whether the treatment has significant side effects, including in combination with the treatments I am already using. If it isn't or the risk seems acceptable, I give the treatment a short trial. This has been very successful in my case, to the point where I am more or less functionally recovered, and a significant part of this has been through treatments that affect the gut.
 

hmnr asg

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This has been very successful in my case, to the point where I am more or less functionally recovered, and a significant part of this has been through treatments that affect the gut.
My cfs started with gut issues actually. After having a meal at a restaurant I had severe abdominal pain and gas for a week before one morning I woke up and my world had turned upside down and I could barely move.

Could you give examples of these treatments ?
I have tried probiotics ( no effect ), two rounds of rifaximin ( small effect while taking the medication). Other than that I haven't found anything to address the gut.
 

msf

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Mine too. It was a Yersinia infection in my case (specific symptoms matched and IgA positive for several years).

I found probiotics had a negative effect when my gut was very messed up. Rifaximin was hard to tell. Metronidazole had a very clear negative effect in that it affected my gut so adversely I couldn't finish the prescribed course, and also caused me to be unable to digest fat for a few months (probably by killing off bile acid producing bacteria), but it was only a few weeks after I took it that I was able to go walking all day in the hills on successive days, when a year ago I would find half an hour's walk on the flat taxing enough. So I think it probably did have the effect it was prescribed for (to alter the gut microbiome).

The most effective treatments I have tried all have some effect on the gut (this is in the order I tried them):

1.) FODMAP diet + Trazodone. The former made an immediate impact straightaway, to the point that it wasn't even a tough choice sticking to the elimination diet for about a year. I have since worked most foods back in, with the exception of gluten, but when my gut gets messed up again (often a consequence of drinking too much), I go back to a fairly strict FODMAP diet since it is so effective. I put these together because I find I need to both take Trazodone and stick to a suitable diet to sleep normally. As with skullcap (see below), if my gut is too messed up from diet or exercise the Trazodone does not work as well.

2.) IV antibiotics for Yersinia, I felt much better after the first course, then slowly relasped, before the second round I believe got rid of it (specific symptoms went away, and unlike the first time didn't come back). The general effects of this treatment on the body were a bit like a more clearcut version of the Metronidazole, in that I felt less lactic acidey and that I had more energy to do things.

3.) Chinese skullcap (I take astralagus and peony root together with it). I first I took this based on the theory that it would help with the complex V energy problems in ME, but I am starting to think it has at least some of its effect on the gut directly (this could still be by changing the energy metabolism of gut cells). However, I still prefer my previous interpretation overall as it only seems to work its magic when my gut is not messed up (for more about this see my blog or the thread I started on skullcap). This has allowed me to exercise normally again.
 
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My cfs started with gut issues actually. After having a meal at a restaurant I had severe abdominal pain and gas for a week before one morning I woke up and my world had turned upside down and I could barely move.

Could you give examples of these treatments ?
I have tried probiotics ( no effect ), two rounds of rifaximin ( small effect while taking the medication). Other than that I haven't found anything to address the gut.
I'm in a similar boat, though my gut issues preceded my ME/CFS by years. Nonetheless, I feel like my ME/CFS is almost certainly due to my gut issues, in whole or in part. I've been through quite a few gut specific treatments without anything working particularly well. Eventually I found out I have small fiber neuropathy, which can definitely cause or exacerbate GI problems due to its effects on the autonomic nervous system, so it may be that I will only improve once that condition is treated effectively, through IVIG or the like.

One treatment I think you should look into is serum bovine immunoglobulins (SBI). The thought is that taking immunoglobulins orally, they bind to bacterial LPS which both increase gut permeability due to inflammation as well as specifically leading to systemic symptoms like fatigue, pain, etc. You can get a doctor's prescription for SBI, marketed under the name Enteragam, but it's a little expensive, and there are non-prescription versions available on the internet. A related product is colostrum, which also contains other proteins, but if you have problems with dairy or lactose it may not be the best option. For me, Enteragam did improve symptoms initially but lost effectiveness. Hopefully it might work better for you.

When it comes to supplements that affect gut barrier integrity, probably the major target is the tight junction. Tight junctions are the gaps between epithelial cells whose permeability are regulated by various proteins, including claudins, occludin, cadherin, etc. One of the most interesting tight junction regulators is berberine, which also has fairly potent antibacterial effects, and so may benefit people with SIBO or other gut flora overgrowth issues. Quercetin also stabilizes tight junctions, in addition to being a mast cell stabilizer, which also may benefit gut permeability since histamine has inflammatory effects which reduce tight junction continence.

Some other supplements which supposedly improve tight junctions include resveratrol, curcumin, magnolia extract, skullcap extract, and raspberry polyphenols. From a dietary perspective, vitamin D is an important tight junction regulator, as are short chain fatty acids such as butyrate. Ideally, a healthy gut flora produces enough butyrate for this purpose, but if you have gut flora issues, some people seem to benefit from taking butyrate supplements.

Another possibly-overlooked part of gut barrier integrity is the mucus layer. The mucus layer is the first line of defense between the intestinal lumen and the epithelium - its upper layers harbor a good proportion of the gut flora, while the lower layers are nearly sterile. Mucus production is impaired in a variety of gut-related issues, including infections. I've recently turned my sights towards this target since I've had recurrent C. Diff, which is known to reduce mucus production. One possible solution would be to supplement some kind of demulcent, like slippery elm or marshmallow root, to form a physical barrier between the food you ingest and your epithelium, sort of a substitute mucus layer. However, these supplements form a gel out of complex carbohydrates/fibers, which might have unpredictable effects on the gut flora.

The mucus layer is formed primarily from mucin, which is a protein. I read somewhere that supplementing the specific amino acids that comprise mucin (proline, threonine, serine, and cysteine) actually upregulates mucus production, and I'll be trying that soon. I haven't found too many other convincing strategies for improving mucus production though - there's a lot of literature on the role of cytokine regulation, but it's kind of convoluted and doesn't lead to any clear answers for me. One pharmaceutical that came up in my search is Mucosta (rebamipide), which is used in various Asian countries to treat gastic ulcers. It seems like it may have a high rate of side effects though, so I'm a bit skeptical of it.
 
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