Is ME/CFS something to do with Butyrate?

Jonathan Edwards

Jonathan Edwards

Senior Member (Voting Rights)
I am just wondering about butyrate again.
The Beentjes paper picked out butyrylcholinesterase.
Bacteria make butyrate and this is very fashionable in theories linking gut immunity to brain. I am sceptical about detailed differences in microbiome but maybe butyrate in general is part of the story.
The DecodeME gene linked to gamma delta T cells (Butyrophilin 3A2) involves butyrate in an innate recognition interaction I think.
Sodium oxybate and butyrate influence GABA levels in brain.

I am tending to think that some particular neurotransmission pathway in brainstem/hypothalamus is crucial and it would be nice if that linked to an immune cell trigger or perpetuation story. Neuropeptides might be involved but butyrate keeps coming up and maybe the link to gut immunity is crucial after all?
 
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Jonathan Edwards said:
The DecodeME gene linked to gamma delta T cells (Butyrophilin 3A2) involves butyrate in an innate recognition interaction I think.

I am tending to think that some particular neurotransmission pathway in brainstem/hypothalamus is crucial and it would be nice if that linked to an immune cell trigger or perpetuation story. Neuropeptides might be involved but butyrate keeps coming up and maybe the link to gut immunity is crucial after all?
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What I've understood so far:

BTN3A2 is not directly involved in binding phosphoantigens. Instead it "helps" BTN3A1 to do that.

BTN3A1 is part outside, part inside the cell. The inner part binds phosphoantigens. The outer part changes upon binding and BTN3A2 ensures the right presentation. The T cells can sense that change.

I don't understand why increased expression of BTN3A2 would lead to immune tolerance or how it could fit into a perpetuation story.

My opinion on butyrate is that eating a diet rich in vegetables is beneficial, which seems like it would fit with the dietary fiber, butyrate, immune tolerance, positive effect on health story. If I don't eat enough vegetables my gut begins feeling mildly inflamed and my overall function declines.
 
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Hoopoe said:
My opinion on butyrate is that eating a diet rich in vegetables is beneficial, which seems like it would fit with the dietary fiber, butyrate, immune tolerance, positive effect on health story. If I don't eat enough vegetables my gut begins feeling mildly inflamed and my overall function declines.
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You may be right. I think lots of vegetables keeps me well too.
But I don't want to go down the road of saying that the cure for ME/CFS is going to be eating more broccoli. I doubt it would do anything critical. But butyrate might be a clue to what really needs doing.
 
Paradoxically to this theory, I’ve found ever since I had ME/CFS I’ve been craving vegetables much less. Much more fruit and meat.

But due to circumstances outside my control, I’ve rotated through a bunch of diets and found that it has zero effect on my functioning. Except perhaps my acid reflux.
 
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Why are all these things named the way they are? I have some recollection that butyrylcholinesterases can have a broad affinity for longer chained molecules not necessarily just of the butyrylated variety. I googled this the other day about the butyrophilins and I think it said they were named after where they were discovered rather than anything to do with the molecule butyrate. I may be wrong
 
Yann04 said:
Paradoxically to this theory, I’ve found ever since I had ME/CFS I’ve been craving vegetables much less. Much more fruit and meat.

But due to circumstances outside my control, I’ve rotated through a bunch of diets and found that it has zero effect on my functioning. Except perhaps my acid reflux.
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As a vegan who pretty much only eats whole foods and whose diet is 99% the standard list of things promoting butyrate production... I am pretty confident that what I eat does FA to help my ME/CFS.

...unless of course I would be worse off were I to start eating less veg. If that's the case... yikes.
 
A previous discussion on butyrate:

Andy

Thread 'Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue..., 2023, Guo,Lipkin et al'

Study now published, see https://www.s4me.info/threads/prepr...toms-2021-guo-lipkin-et-al.23117/#post-459929 for abstract and link.

Preprint: Deficient butyrate-producing capacity in the gut microbiome of [ME/CFS] patients is associated with fatigue symptoms, 2021, Guo,Lipkin et al

Abstract
Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, debilitating disease of unknown cause for which there is no specific...
  • Andy
  • butyrate dysbiosis fatigue gut microbiome lipkin me/cfs microbiome
  • Replies: 37
  • Forum: ME/CFS research
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chillier said:
Why are all these things named the way they are? I have some recollection that butyrylcholinesterases can have a broad affinity for longer chained molecules not necessarily just of the butyrylated variety. I googled this the other day about the butyrophilins and I think it said they were named after where they were discovered rather than anything to do with the molecule butyrate. I may be wrong
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A good question. Maybe they were discovered in Butyl City, Kentucky.
I used to ask the students what was the chemical relation between urate and urea - and we all had a laugh when the penny dropped that there wan't one - just they were discovered in urine.

Who knows the answer?
 
Apparently GABA acts on ion channels.

If it's acting on those for skeletal muscle, suppressing activation as soon as people start doing something, it might explain why people with ME/CFS have to abandon making breakfast this instant and sit or lie down, but are able to get up and finish the job after a short rest. Before having to sit down again.

Why and how it would do that is the question, I suppose!
 
Jonathan Edwards said:
So members don't find it a wonder cure.
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I'd agree that there's no evidence on that thread that we do, but what people were discussing there was either taking butyrate supplements (and butyrate isn't know to make it past the stomach?) or following a high-fibre diet, which wouldn't necessarily help produce much butyrate if there was dysbiosis.

I wonder if there's better-quality evidence about this somewhere. I don't know if the amount of butyrate in the gut can be measured reliably? (Sorry if this is a bit of a rubbish suggestion but I haven't followed this thread properly.)
 
Jonathan Edwards said:
Is dysbiosis a real thing?
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I wasn't aware that there was any doubt that dysbiosis was a thing but I'm not in a position to defend the concept!
Jonathan Edwards said:
I have no idea, but despite studies showing people with ME/CFS have a few more thingammadodgemacocci than other people I am sceptical that there is anything dreadfully wrong with their gut contents.
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Above my pay grade but I'd have thought someone would have done a review somewhere, particularly since Lipkin and Norwich have been so interested in it.
 
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