Comment by jinder | Hacker News Reader

Comment by jinder | Hacker News Reader

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Famotidine an old school H2 antihistamine used for acid reflux (pre PPIs), was found to have an additional mechanism of action via activation of the vagus nerve to inhibit pro-inflammatory cytokines in covid (via alpha 7 nicotinic acetylcholine receptor (α7nAChR) signal transduction - https://molmed.biomedcentral.com/articles/10.1186/s10020-022...).

It has also been used quite extensively to combat post-covid neuropsychiatric symptoms.

I think the link here is that increased LPS/endotoxin production by your microbiota can induce acid reflux, cause neuroinflammation and psychiatric symptoms. Low acid production itself can result in a more inflammatory microbiome further exacerbating the problem. Long term fix would be working on the migrating motor complex, improve motility/gastric emptying and rebalance the microbiome by reducing gram-negative bacteria/pathobionts and increasing butyrate production via selective feeding. [I'm not a doctor, this is just the direction I've been working on things myself]

That's interesting about famotidine. This is also a treatment for MCAS, which is probably under-diagnosed because it's kind of obscure and the diagnostic criteria kind of suck currently. It can reduce stomach acid, so my doctor and I decided against using it as the first option in treatment, but may reconsider even though the alternative seems to be working. Thanks for the link and explanation.

Can you share any relevant resources or ideas you've gotten on reducing the opportunists and increasing butyrate production? I've coaxed and cajoled my MMC and other digestive processes back into shape, or so it seems, but am struggling on the microbiome angle. It's tricky because the list of foods that trigger symptoms is insanely long, so it's hard to get creative and experimental as far as that goes.

Some people really do have mast cell issues, but everyone and their dog thinks they have MCAS these days and it's questionable in my opinion. Often a diagnosis will be based on whether any of the MCAS-drugs work (rather than testing which is very problematic for MCAS). But as you see in the linked paper famotidine was effective in mice genetically engineered without mast cells, so at least in that instance it's not a mast cell issue.

The tricky thing with increasing butyrate production is that everyone's gut dysbiosis is different - and therefore, a prebiotic that works for one person may make someone else's condition worse. For example, I have big blooms in my Prevotella Copri population which would consume Inulin and make my butyrate production worse - but in people without a Prevotella Copri overgrowth, Inulin would improve their butyrate production.

I would look into 16S microbiome testing (I use Biomesight) and use that as a guide, as well as slowly trialing interventions and monitoring symptoms. None of this is perfect and you kinda have to be on the bleeding edge of science/alternative medicine to figure things out.

Look into PHGG for increasing butyrate production

https://www.sciencedirect.com/science/article/pii/S175646462...

One thing that really helped me was just going to the gym. Basically strengthening my core improved my posture so that my esophagus isn't as crooked due to shitty posture.

I had years of dysbiosis type problems and found that the other main H2 blocker, Ranitidine, helped with my symptoms. Luckily I didn't take it that often or for too long, as it was found to be dangerously contaminated with a carcinogen when stored for too long. But that's not the point. The point is that an H2 blocker strangely offered relief.

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