Is ME/CFS something to do with Butyrate?

Other than treating H pylori and parasites I don’t think there really is (naturopaths will throw a fit here). There’s a vague idea of unbalanced flora but no one right now is in a position to “fix” it or say it’s 100% wrong.

I had a friend who worked at Ubiome, they made tests for dysbiosis and gave medical recommendations for it(this was the big no no). First of all every test showed different results depending on the week you took the test and secondly they got raided by the FBI eventually for those medical recommendations without FDA approved tests. There’s also a Great Wall Street journal podcast on it.
 
I think Butyrate also came up is some of OMF/Ron Davis’ work when they were working on the metabolic trap hypothesis. It may be in a video as opposed to in something that got published. I’ll see if I can find it.
 
Utsikt said:
@ME/CFS Science Blog wrote this:

For the proteomics, the following seem to be the values that stand out most. I've extracted the following values from the data (Using direct effects).

Name(abbreviation), cohen_d_raw_data, z_value_modelled, corrected_p_value

Males
Butyrylcholinesterase (BCHE), 0.796, +5.3, 0.000313,
(…)

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Is this an increase in BuChE?

Pyridostigmine/Mestinon inhibits AChE and BuChE afaik
 
There were some mentions of butyrate in the NIH deep phenotyping study, and in the symposium about the study:

ME/CFS Symposium – May 2, 2024
[Dr. John McCullough] When we look at which, what other microbial species, which are either enriched or depleted, so there are about in the order of about 200 different species that we found overall in samples. If we look at which ones are increased in healthy donors, and which ones are increased in ME/CFS samples, we find that there are about 25 different species, which are enriched in either group. [...]

Not going to go through all of them, but suffice to say that several of these species, especially those which were enriched in the CFS samples were also found to be enriched in other studies. That confirms, although it is not exactly the same species overall, this confirms the previous studies that involve the microbiome were all gram positive members of the phylum firmicutes.
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[Dr. Avindra Nath] The microbiome, as you heard from Dr. McCullough that while there was no smoking gun per se, there is, they didn't really find much alpha diversity but there was beta diversity. He pointed out that multiple different types of taxonomic types of bacteria were affected, one that has been talked about quite a bit is butyrate-producing bacteria being decreased. I think that is important because what we found was that in the spinal fluid also of these patients there were decreased levels of butyrate.
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Figure S20D from the study's supplementary info seems to be about the specific bacteria in the gut. It looks like increases and decreases of many different species, so I'm not sure which specific species he's referring to.

Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome, 2024, Walitt et al
Metabolomic analysis of cerebrospinal fluid also showed group differences (Fig. 6h). [...] Decreased glutamate, dopamine 3-O-sulfate, butyrate, polyamine, and tricarboxylic acid (TCA) pathway metabolites were noted in PI-ME/CFS participants (Supplementary Data S14A).
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[Cerebrospinal fluid, page 16 of supplementary information] Analysis of branch chain amino acids showed a decrease in butyrate, as well as decreased metabolites related to the tricarboxylic acid pathway in PI-ME/CFS participant
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A bit of a sideline, just noting the involvement of iron in butyrate metabolism (HFE is one of the tier 1 candidate genes)

As I understand it, iron status inside the gut affects how much butyrate bacteria produce. Butyrate levels, in turn, regulate iron metabolism. So it’s conceivable that HFE being up- or downregulated could mess with that loop and – maybe – lead to altered butyrate levels

I wrote a more detailed post in the HFE thread
 
Interesting point on no clinically obvious major effect on brain function post colectomy. I don't think we've got studies on this to be sure and there may be up to decades latency so we might not pick it up. It's probably hard given that younger adults (eg IBD/UC) would be exposed to all sorts of immunomodulators, and older adults might be similar via the cancer/chemotherapy scenario.

It does sound speculatively relevant to some conditions but it's not clear if what if any relationship there'll be with ME/CFS. Eg a review this week for ALS —

The Emerging Role of the Brain–Gut Axis in Amyotrophic Lateral Sclerosis: Pathogenesis, Mechanisms, and Therapeutic Perspectives
Yang; Eun Jin

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Although genetic and environmental factors are established contributors, recent research has highlighted the critical role of the gut–brain axis (GBA) in ALS pathogenesis. The GBA is a bidirectional communication network involving neural, immune, and endocrine pathways that connect the gut microbiota with the central nervous system. Dysbiosis in ALS disrupts this axis, leading to increased intestinal permeability, neuroinflammation, and excitotoxicity. Notably, reductions in butyrate-producing bacteria, alterations in microbial metabolites, and enhanced NLRP3 inflammasome activation have been observed in patients with ALS. These changes may precede motor symptoms, suggesting a potential causative role.

Interventions targeting the microbiome, such as dietary modulation, have shown promise in delaying disease onset and reducing inflammation. However, the clinical evidence remains limited. Given that gut dysbiosis may precede neurological symptoms, microbiota-targeted therapies offer a novel and potentially modifiable approach to ALS treatment. Understanding the role of GBA in ALS will open new avenues for early diagnosis and intervention. Further clinical trials are required to clarify the causal links and evaluate the efficacy of microbiome-based interventions. Understanding the brain–gut–microbiota axis in ALS could lead to new diagnostic biomarkers and therapeutic strategies.

Web | PDF | International Journal of Molecular Sciences | Open Access
 
SNT Gatchaman said:
Interesting point on no clinically obvious major effect on brain function post colectomy. I don't think we've got studies on this to be sure and there may be up to decades latency so we might not pick it up.
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Surely butyrate from a removed colon does not hang around for years? Days maybe. I have come across a number of people who have had total colectomy or defunctioning colostomy for long periods. There wasn't the slightest indication of any effect on the brain. If there was I think it would have been noted decades ago. After all, a total colectomy is a fairly black and white situation. If colonic bacteria derived butyrate is important it ought to be barn door obvious. And nobody has ever mentioned a problem in my medical lifetime.

SNT Gatchaman said:
Eg a review this week for ALS —
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Judging by the abstract that is just a rehash of empty memes and speculations.
 
Jonathan Edwards said:
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.
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Jonathan Edwards said:
It is intriguing that Google and other sources all say that brain butyrate comes from the colon. But people who have had a total colectomy don't have major brain problems. Clearly the brain is not dependent on the microbiome for good functioning.
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If it is true that people can live just fine without their microbiome producing butyrate that would point to one or more of three possibilities (that I can think of)
  1. there’s another currently unknown way of making butyrate in human cells; it seems unlikely the body would want to rely on butter consumption
  2. butyrate is not essential, more a nice-to-have that makes things go more smoothly
  3. the body has alternative pathways, maybe analogous to how cells like to run on glucose but in case of needs must they can easily switch to fats or even proteins​
The first option seems unlikely?

The second option could mean that while a lack of butyrate alone isn't a problem it could be the last straw that nudges some T cell or GABA mechanism over the edge into dysfunction if it happens to be already fragile for other reasons

The third option raises the questions of what those alternative non-microbial pathways used by for example gamma delta T cells and Gaba metabolism might be, and how they might be malfunctioning in ME. No idea if there even are any biologically plausible candidates
 
Jonathan Edwards said:
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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Is there any place for the idea that butyrate in the gut helps prevent leaky gut, and having stuff leaking from the gut into the bloodstream would have immune effects? Do people with colectomies have immune issues? A random googling pulled up this paper, which suggests they're at higher risk of autoimmune disease (but lots of other papers might suggest otherwise).
 
Just to chyme in @Jonathan Edwards I also a couple months back (before discovering the Daratumumab hype train with Fluge and Mella which I am fully onboard), I was on the butyrate hype train.

I did a very comprehensive 1 month regimen to absolutely boost my butyrate to high levels. It was:

* Butyrate supplement
* Butyrate producing probiotic
* Butyrate boosting prebiotics
* 1 jar of kefir everyday.

I threw the book at it. Guess what? Zero changes to symptoms at all. Just diarrhea from spamming the butyrate and kefir.

I am quite sure my intestine was overflowing with butyrate, especially with Kefir. But I had zero changes to symptoms. So n=1, probably nothing.
 
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