Should we be trying to increase butyrate in the gut?

Sasha

Sasha

Senior Member (Voting Rights)
I've just been reading The Anti-Viral Gut by gastroenterologist Robynne Chutkan, which focuses quite a bit on Covid. In it, she says that in a large study of Covid patients, the composition of the gut microbiome predicted the development of severe respiratory symptoms and death with 92% accuracy; and that Covid disease severity is inversely related with the levels of Faecalibacterium prausnitzii (a butyrate-producer) in the gut.

She says that short-chain fatty acids (SCFAs) help orchestrate immune equilibrium (preventing an overblown response to infection) and help tighten up the gut epithelial barrier, which stops virus leaking through it; and that the more F. prausnitzii you have in your gut, the less susceptible to viral illness you will be.

The Guo et al. 2023 study, 'Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS' (other authors included Lipkin, Hornig, Vernon, Bateman, Montoya and other big ME/CFS names) found:

NIH study said:
Faecalibacterium prausnitzii and Eubacterium rectale, which are both recognized as abundant, health-promoting butyrate producers in the human gut, were reduced in ME/CFS. Functional metagenomics, qPCR, and metabolomics of fecal short-chain fatty acids confirmed a deficient microbial capacity for butyrate synthesis. [...] The abundance of Faecalibacterium prausnitzii was inversely associated with fatigue severity. These findings demonstrate the functional nature of gut dysbiosis and the underlying microbial network disturbance in ME/CFS, providing possible targets for disease classification and therapeutic trials.
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In this webinar, Lipkin discusses these results and says:

Lipkin said:
One of the things that I would be most excited to try to address would be to identify those individuals who have very low levels of butyrate-producing bacteria, and find out whether by using prebiotics and probiotics which are really fairly benign, whether or not we can show some sort of an improvement in symptoms.
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Dr Chutkan says you can boost your levels of F. prausnitzii by eating a salad every day (she didn't say why - maybe for the bugs they carry) and eating foods rich in the prebiotic inulin (onions, garlic, leeks, asparagus, etc.). (You can also buy inulin powder, but she doesn't mention that.)

I'm conscious that Ken Lassensen has famously managed to put himself into remission several times with a gut approach. He puts a lot of information out there and says that other people have reported improvements from his approach but I found his website overwhelming at a first glance and don't know what he does.

Anyway, what do we think? Should be trying to increase our F. prausnitzii and butyrate? Is a trial under way? If one isn't, should we be pushing for one?
 
Sasha said:
Is butyrate a thing that ever makes people worse?
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This is ME we're talking about, so pretty much anything has potential to make ME worse. Strengthening the intestinal barrier might reduce some signal that was keeping some other mechanism under control, resulting in worsening. With ME, I expect that most treatments that provide some benefit for some people will also make at least a few other people worse. If you did a butyrate supplement study with 1000 PWME, I would be really surprised if none of them reported worsening. There are just too many complex interactions involved.

The question is whether butyrate supplementation is worth the expense of a proper trial. I expect there are plenty of PWME who have followed butyrate-producing diets or consumed lots of butter (I don't know whether that butyrate reaches far down the digestive tract). If hundreds of those people reported major improvements from butyrate-boosting, then it might be worth a proper trial. Without that observational evidence, it's just another theory for a treatment that might provide a benefit.
 
Creekside said:
The question is whether butyrate supplementation is worth the expense of a proper trial. I expect there are plenty of PWME who have followed butyrate-producing diets or consumed lots of butter (I don't know whether that butyrate reaches far down the digestive tract). If hundreds of those people reported major improvements from butyrate-boosting, then it might be worth a proper trial. Without that observational evidence, it's just another theory for a treatment that might provide a benefit.
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I don't know that people realise when they're following a butyrate-producing diet, so I think it would be hard to get that kind of observational evidence. I doubt that most people know what butyrate is.
 
Anecdotally, I made butyrate friendly dietary changes and took a butyrate producing probiotic strain using a (unproven of course) stool sample test.
It did have a very positive effect on my gut symptoms, but disappointingly did nothing significant for my ME severity or functioning level. Perhaps I was a bit more stable and had a better spell, though that could have been also be a knock on from reduced gut symptoms.
 
Sasha said:
Is butyrate a thing that ever makes people worse? (Honest question! I've only ever seen it mentioned as something benign.)
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I googled 'butyrate diet'. The second hit was a study in mice finding that a high butyrate diet made them more susceptible to e coli, and the third was the Cleveland Clinic saying high butyrate levels can cause bloating in those with a 'sensitive gut'.
 
There is a NIH funded trial for Gulf War illness that will test this:

Microbiome targeted oral butyrate therapy in Gulf War multisymptom illness
The goal of this clinical trial is to determine if a Butyrate formulation that consists of butyric acid as calcium and magnesium derivatives in a single oral capsule administered twice a day is effective in increasing physical functioning for Veterans with Gulf War Illness. The secondary outcome will focus on the drug's role in (a) restoring gut microbiome and virome (that have been found altered in GWI veterans), (b) decreasing gastrointestinal disturbances (constipation, diarrhea, pain) (c) decreasing chronic fatigue, (d) decreasing systemic inflammation such a blood levels of proinflammatory cytokines and (d) a decrease in cognitive deficits. The clinical trial involving butyrate on Gulf War Illness veterans will be conducted in three sites across the nation.
https://reporter.nih.gov/search/dw8kmGn1VkulvUJ3tkikaQ/project-details/10784587
 
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