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Butyrate induces HSV/EBV/HHV6 reactivation - Reason why some react negatively to fiber/probiotics?

Wonkmonk

Senior Member
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1,006
Location
Germany
I have seen that it seems to be quite firmly established that butyrate (butyric acid) is a strong inducer of herpes virus reactivation and replication, including EBV, HHV6 and HSV1.

Studies:

https://www.ncbi.nlm.nih.gov/pubmed/11059774

https://www.ncbi.nlm.nih.gov/pubmed/9753061

https://www.ncbi.nlm.nih.gov/pubmed/17360760

https://www.sciencedirect.com/science/article/pii/0042682286902187

http://grantome.com/grant/NIH/F32-CA165705-03

http://jvi.asm.org/content/88/14/8028.full

https://www.ncbi.nlm.nih.gov/pubmed/220786

Butyrate is produced by probiotic colonic bacteria by fermenting fiber and prebiotics. I have also seen a study which I can't find anymore that butyrate produced by colonic bacteria does enter the blood stream.

I am wondering if this could be the reason why there are many reports of Herxheimer-type reactions to probiotics and also some reports of getting worse with high intake of fiber. I think high fiber intake (10-20g Psyllium husk) might make me worse, but I have been wondering why this is the case.

Could this be an explanation?

There is also at least one report on PR from someone who got worse when taking butyrate directly as a supplement (cc: @ebethc).

https://forums.phoenixrising.me/index.php?threads/does-butyrate-make-you-sick-at-first.32842/

Usually we think of fiber and probiotics as healthy food choices and intake is encouraged, but maybe it should better be limited in order to lower the amount of butyrate.
 

Runner5

Senior Member
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323
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PNW
I had bad reactions to probiotics, but it's kinda hard to tease out what is being caused by the probiotic and what might be -- say a food reaction, or a bad day. I've had a rough GI for so long, different day, different stuff I'm dealing with - So I was never quite sure but I stopped taking them finally (started off an on from '95).

I cannot take psyllium, Acacia or any of the fiber supplements they absolutely do me in. Those snack bars called "Fiber One" -- OMG -- THE WORST. It might as well be a prescription for pain in my book. I can't really do granola or whole wheat either.

I eat a very high fiber diet. I probably eat 3-5x more fiber then the average American (which I suppose isn't that tall of a goal post? haha) and that prebiotic fiber that I eat now that kicks great butt in my GI and I've feel a little better every day. I eat beans everyday, blueberries everyday, brown rice everyday, loads of greens 3-8 cups worth, bananas, apples, pineapple, loads of squashes, corn & quinoa -- I've just been loading up on the fiber.

I just started in May and it was a slow start really as the GI adjusted, I had some improvements and no harm so I stuck with it. But for the last couple of weeks I really have just felt better every single day and I think it's the microbiome having a bit of a party. Had a little fuss with canned tomatoes but in my stomach not my lower GI, no GI sores.

It's probably the first time I have a reliable working happy GI in years.

I do the Dr. Gregers Daily Dozen, the only thing I don't always fit in are cruciferous. I really like cabbage but in a day full of fruit and veggies it's hard to get all of them in.
 

Learner1

Senior Member
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6,305
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Pacific Northwest
Usually we think of fiber and probiotics as healthy food choices and intake is encouraged, but maybe it should better be limited in order to lower the amount of butyrate.
I'm not understanding your equivalence of fiber and probiotics and butyrate. And, butyrate seems ubiquitous enough - is it really tge sole thing causing herpes virus reactivation in these studies?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070119/

From the abstract:

The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine.
 

Sidny

Senior Member
Messages
176
I remember reading somewhere someone using sodium butyrate + antiviral herbs/etc to draw out virus from the nerves and finish them off. Not sure if it worked though.

That’s interesting, do you think you’d be able to dig up a link for that?
I believe an hsv infection trggered my me/cfs as i contracted a primary infection at the onset of my illness. If not at least the main trigger I’m sure contributed to the overall picture.

Seems like a catch 22 though, I’m currently experiencing severe gastric dysmotility/gut palsy and I’d imagine fiber might help regulate things a bit but it seems at the cost of fueling the virus. I also have suspected Lyme which is known to paralyze the enteric nervous system as well. Not fun to say the least.

https://forums.phoenixrising.me/ind...es-symptom-new-study-finds.45202/#post-981364
 

Hip

Senior Member
Messages
17,824
it seems to be quite firmly established that butyrate (butyric acid) is a strong inducer of herpes virus reactivation and replication, including EBV, HHV6 and HSV1.

I am wondering if this could be the reason why there are many reports of Herxheimer-type reactions to probiotics and also some reports of getting worse with high intake of fiber.

That's an interesting theory, Wonkmonk.

Although note that viral reactivation may not necessarily be a bad thing in ME/CFS, in the long term; indeed, it could be very beneficial. This is because if you take a virus like EBV, this hides away from the immune system by entering B-cells and then going into latency; but if you could re-awaken all the latent EBV so that it starts replicating, then you would force the immune system to fight and kill EBV, which in theory could entirely eradicate EBV from the body. Similarly for HSV, which goes into latency in peripheral nerve ganglia cells and in other places.

There has been research into latency reversal agents in HIV, as latently-infected cells are the major barrier to HIV eradication from the body.

But certainly in the short term, if butyrate from probiotics or prebiotics is causing herpesvirus reactivation from latency, then you might expect your ME/CFS symptoms to initially get worse.

But the issue about whether or not butyrate from probiotic bacteria is systemically absorbed in colon is important to this discussion; that is examined in the following section:



I have also seen a study which I can't find anymore that butyrate produced by colonic bacteria does enter the blood stream.

This paper says that the short chain fatty acids (SCFA) acetate, propionate and butyrate are all readily absorbed from the human jejunum (part of the small intestine).

However, I cannot find any authoritative source that states whether or not butyrate is absorbed from the colon. But I would not think much butyrate is systemically absorbed in the colon, because butyrate is preferentially taken up by colonic epithelial cells for use as internal energy source (which then promotes epithelial cell proliferation and injury repair). Ref: 1

So the epithelial cells in the colon may absorb and metabolize much of the butyrate made by gut bacteria, before it gets a chance to absorb systemically into the bloodstream.

However it is very likely that butyrate from oral supplements like sodium butyrate, or butyrate from butter, will enter the bloodstream via absorption in the small intestine (in the jejunum). Butter contains around 3 to 4% butyrate in the form tributyrin. Ref: 1



Here are some general notes I made on butyrate:
FOS (fructooligosaccharide) prebiotic increases butyrate concentrations in the large intestine; butyrate helps reduce intestinal permeability. The typical US diet contains about 2.5 grams of FOS a day. A typical Mediterranean diet provides 12 or more grams of FOS a day.

Clostridium butyricum probiotic produces butyrate (it converts lactate into butyrate in the gut). Some ME/CFS patients reported good results with this unique probiotic.

I could not find any details about how much butyrate is synthesized each day by gut bacteria, though someone here reckons 14,000 mg a day, but does not provide a reference.

This study found that butyrate from Clostridium butyricum down-regulated the expression of TLR4 in the colon. TLR4 is the same receptor that low-dose naltrexone blocks, so the benefits of Clostridium butyricum for ME/CFS may come from the same TLR4 mechanism.

Butyrate is a histone deacetylase (HDAC) inhibitor, and HDAC inhibitors have been shown to suppress coxsackievirus B3 growth in murine myocarditis.

I found a potential mechanism by which butyrate might fight the intracellular viral infections in ME/CFS:
  • Butyrate is a potent inducer of cathelicidin inside the cell (ref: 1)
  • Cathelicidin in turn enables TLR3 to respond to the presence of viral dsRNA in the cell
  • When TLR3 detects this viral dsRNA inside the cell, it turns on the intracellular immune response by releasing interferon, which then fights the intracellular infection.
Since ME/CFS is linked to chronic intracellular infections of non-cytolytic enterovirus (which consists of dsRNA), I wonder if butyrate could help fight these chronic enterovirus infections, and ameliorate enterovirus-associated ME/CFS.

Perhaps high doses of butyrate might be a poor man's Ampligen, because Ampligen works by stimulating TLR3.
 
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Learner1

Senior Member
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Location
Pacific Northwest
I remember reading somewhere someone using sodium butyrate + antiviral herbs/etc to draw out virus from the nerves and finish them off. Not sure if it worked though.
Once you have one of these viruses, it'll always be in your system. No such luck in finishing them off...

Perhaps. But there are a whole host of bacteria in your microbiome that produce butyrate, and it's almost impossible to have control over which ones decide to set up shop or leave. This doesn't seem like a variable one can control much, other than avoiding butyrate supplements. And The butyrate supplements I've come across are cal-mag butyrate, not sodium butyrate.

How would you control it? And how would you look at the increased risk if health problems from NOT having its benefits?

Regarding your question, I can't say. I can't claim to have read and understood all these studies. But I think they say butyrate contributes to herpes virus reactivation.
Does it? It seems tgst butyrate is going to be in most people's guts whether they know it or not. Did all these experiments do a full DNA sequencing of the patients' and controls' microbiomes, then only allow people into the study without an ounce of butyrate producing bacteria in their microbiomes?

Just about everyone in the population has been exposed to one or many herpes viruses and just about everyone has butyrate -producing bacteria in their guts. So do all of tgesecpeople have reactivated herpes viruses? This doesn't make much sense.

I'm not trying to be obtuse, but have spent almost 10 years mucking around with stool tests, probiotics and probiotics and it just doesn't seem that clear. I don't doubt the studies that were cited were done, I just think we need to know a lot more before running off to any stong conclusions.
 

Runner5

Senior Member
Messages
323
Location
PNW
@bertiedog -- fastest supper is to open can of pinto beans, heat them up on the stove. They have bags of microwavable brown rice and veggies so those go together pretty well too. I have a large spice collection of stuff to throw in. Dehydrated onion, onion powder, garlic salt are good. Sometimes I soak beans and make up a large batch the next day and eat on them during the week. I do like about all beans and I try to find new varieties I haven't had before like Anazazi (they taste a lot like pinto). I also eat black-eyed peas, chickpeas and lentils. I was surprised to find canned lentils last time I went to the store. If I still ate meat I think a strip of bacon in the beans would greatly enhance things! haha

Sometimes I can find frozen beans. All in all my suppers usually never take more than 10 minutes to fix, sometimes I prep ahead making a large batch of brown rice or beans for the week, but it's all very speedy and comes together rapidly.

Supposedly in a study of a little over 7,000 people they found that eating legumes daily significantly increased health and decreased mortality. The actual study is locked behind a pay wall but I like to think beans are a good time.

(edit: if this is too off topic delete or move to a "Runner5 recipe tip section" ;-P)
 

Wonkmonk

Senior Member
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1,006
Location
Germany
How would you control it? And how would you look at the increased risk if health problems from NOT having its benefits?

As I understand it, most butyrate is produced by bacterial fermentation of dietary fiber and prebiotics (inulin, resistant starch etc.), so lowering the fiber intake to a moderate dose would probably be a way to lower butyrate. You'd then have the adverse health effects of a low-fiber diet, but if lowering fiber intake helps CFS symptoms, it may be worth forgoing the benefits of higher fiber intake and higher butyrate, just like kidney patients need to be on a low potassium diet.

Avoiding probiotics and fermented foods (yoghurt, kefir, olives etc.) would probably also be a way to lower butyrate, because as Hip pointed out, butyrate is produced from lactate and lactic acid bacteria in probiotics/fermented foods produce lactate. Again there is a trade-off because lactic acid bacteria have positive health effects.

But for amelioration of CFS symptoms, both may be a price worth paying IF cfs symptoms get better by avoiding fiber/probiotics.

Does it? It seems tgst butyrate is going to be in most people's guts whether they know it or not. Did all these experiments do a full DNA sequencing of the patients' and controls' microbiomes, then only allow people into the study without an ounce of butyrate producing bacteria in their microbiomes?

I think all were in vitro studies and animal model studies, but I think at least under these circumstances, there seems to be solid evidence that butyrate contributes herpes virus reactivation.

As Hip mentioned, for a healthy person, that may be a good thing and actually lower the amount of infected cells. In fact, this study shows probiotics might lower EBV titers (the mechanism is unclear though, unclear if has to do with the butyrate):

https://www.ncbi.nlm.nih.gov/pubmed/27294502

The question is, what the effect it may have in a CFS patient who has widespread active chronic (probably abortive) herpes virus infection. It's possible that it might make things worse to activate the herpes virus under these circumstances.
 
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Richard7

Senior Member
Messages
772
Location
Australia
I know that in his talk last year Chris Armstrong said that in normal people's guts the SCFAs are mostly used up by the gut. In the PWME/CFS that he studied there was disbyosis that lead to microbiomes that produced excessive amounts of SCFAs that were spilling over into the blood and activating AMPk.

My understanding from MacFabe's research on similar issues in autism (where propionate is seen as the major issue) SCFAs are absorbed throughout the colon, but there is some problem that I cannot quite remember SCFAs absorbed from the distal colon bypassing the liver.

(I have been suffering the other kind of problem, major gut issues following taking antibiotics. I used to - like @Runner5 consume lots of legumes every day and now cannot even manage green peas.)
 

Wonkmonk

Senior Member
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1,006
Location
Germany
In the PWME/CFS that he studied there was disbyosis that lead to microbiomes that produced excessive amounts of SCFAs that were spilling over into the blood

For those whose CFS is caused by a widespread, chronic intracellular herpesvirus infection, this might then indeed be a trigger for reactivation.

In a healthy person with only few latently infected cells, this might be a good thing and clear out some of them. In someone with a widespread infection in various organs and tissues, it might make them worse.

If you have only few infected cells, only few of them get activated by the butyrate at a time and the immune system might be able to deal with it. But if there are lots of infected cells throughout the body, lots of cells are activated by the butyrate and the immune system might not be able to control the reactivation. Then people would feel worse (even permanently if the reactivation leads to a greater number of cells infected than before).
 

Runner5

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Location
PNW
@Richard7 -- I still have FODMAP issues and can't eat peas so I feel the pain there, they were always that one food that wouldn't digest - I just added chickpeas and lentils late last week in a tiny amount and they might not make the cut, it just depends. But you might try some digestive enzymes, I use a general digestive enzyme and the pineapple one Bromelain. Something I enjoy is eating Gin Gin candies. They're chock full of ginger. At first it's like "Omg this is so spicy I'm going to die..." then it's like, "give me more!" Ginger usually helps my GI a lot, it's not a cure, and I think it has enzymes in it or something, but I eat it everyday and I gnaw on Gin Gin candies.

I don't even like bananas but that was where I started because I never had a problem with banana. I had to advance slowly into beans, haha, it takes a little bit for the GI to adapt to those.

If you have FODMAP issues the number one problem foods are Onion and Garlic. At first I was in disbelief of this list. I love cooking with onion and garlic! But when I cut those two items out my gurgles go away. I usually add them back in every so often because veggies taste nicer with garlic, but I have to be careful, usually some onion powder or garlic powder is what I'm limited to.

What would happen for me is say my GI didn't like garlic, but soon instead of just reacting grumpily and gurgling every time I had garlic it started reacting to everything - non-stop - 24/7. When I went to the doctor and said "everything bothers my GI!" the doc thought I was crazy. When it first started having issues back in the day, I had to teach high school. I was worried a bad accident would befall me in front of teen boys. It was so embarrassing.

Good luck Richard, hope your GI feels better soon. If you find out any tips for me, I'm still trying to figure it all out myself!
 

ebethc

Senior Member
Messages
1,901
Are all prebiotics problematic? Specifically, I'm curious about Larch (arabinogalactan) and GOS.

Do all beans increase butyrate?

I can't tolerate inulin at all, and only small amounts of butter (which is supposedly a good way to increase butyrate).. I took butyrate supplements and couldn't tolerate them AT ALL which I've never understood... All I've read is the benefits of butyrate, but I've never seen anything on why it would make you sick...thoughts?

Larch is helpful for my IBS-C, but I don't know if it's screwing up something else..
 

Richard7

Senior Member
Messages
772
Location
Australia
@Runner5 thanks for the feedback.

I am having plenty of fibre from fruits and vegetables. I seem to have just become much more sensitive to foods, suddenly part way through the course of antibiotics I could handle neither legumes nor dairy.

Which is a problem as the way I had planned to manage being horizontal for a couple of weeks was canned beans, cheese and and veges I could eat raw and whole.

I have improved by taking lots of probiotics and can now manage dairy, or at least probiotics grown on milk as DIY yoghurt, but the thought of beans or chickpeas turns my stomach.