Improve FMT effectiveness with mucus and biofilm dissolver? N-acetyl cysteine (NAC)

Asclepius

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I've been thinking of ways of improving the efficiency of FMT and thought about how bacteria create biofilm (a polysaccharide structure) and how they live in the mucus layer in the intestine.

Biofilm structure and maturation:

fcimb-12-1003033-g001.jpg


Mucus layer:

1-s2.0-S1931312823002196-gr2.jpg


Maybe a reason for why FMT doesn't always work is because the new bacteria can't penetrate deep enough into the mucus and that these structures acts as protection for the pre-existing bacteria that already live there. What I've noticed from my FMT's is that whatever effect I've experienced from the treatment has been the first to go when I've tried new experiments (diet changes, herbals etc.) and the old symptoms persists which I hypothesise is because the transplanted microbes only manages to colonize the top of the mucus layer and the old microbes live deeper down which gives them greater resilience.

N-acetyl cysteine (NAC) is an amino acid which has both biofilm disruptive and mucus thinning properties and is commercially available so I've been thinking of what happens when combining it with FMT. Maybe it opens up for better engraftment of the donors biome, or maybe it's dangerous.

Disruption of the mucus layer can lead to colitis and cancer though so that's a big risk that needs to be taken into consideration.

A-Environmental-effects-on-mucus-barrier-function-The-healthy-colon-features-a-layer.png


But using low dose NAC short term seems rather safe and has been shown to have some positive effects on the immune system, blood sugar etc. I've read anecdotes of people using it long term who developed histamine intolerance though, so I'd never use it for an extended period of time. But this raises the question whether this is safe and could it have some positive effect on FMT?

My own experience with FMT is that bowel prep does make a difference (tried same donors with and without prep) where osmotic laxatives have been the most impactfull. So another thing to take into consideration is what happens when you combine NAC and laxatives?

I could see 3 possible scenarios for applying NAC:

NAC before bowel prep, no NAC during day of FMT:
So this strategy means that you only take NAC leading up to the transplant, I don't know if it's necessary to do multiple days of NAC or if same day as laxatives is enough. There are no studies on combining osmotic laxatives with NAC so we don't know what effect it could have. It could have the effect that it opens up the biofilm and mucus which together with the laxatives flushes bacteria out which could be helpful leading up to the transplant, or it could be absolutely detrimental and destabilise your entire microbiome. The reason for not taking NAC on the day of treatment is because it can interfere with the adhesion of bacteria which in theory could make it harder for the new bacteria to colonize. NAC also possess some antimicrobial properties which could harm the new bacteria depending on its spectrum of activity and the donors biome.

NAC before bowel prep + NAC during day of FMT:

Only difference here is to also use NAC on the day of the transplant and the reason for this is that new biofilm formation happens in just a few hours. If the amount that forms in 1 day is significant enough to impact the transplant we can only speculate about. By taking it on the same day we remove that concern and also get the mucus thinning property which might result in deeper colonization.

Bowel prep without NAC, NAC only during day of FMT:
Since there are no studies on combining osmotic laxatives with NAC, skipping it removes that risk. By only taking it on the day of the transplant we're only dealing with the interaction of NAC and FMT (which could still be dangerous though).

I'm NOT encouraging others to try this, I just want to open this up for discussion.

Could NAC be useful for FMT?
Is it too dangerous to try?
 
I remember reading something on this topic but my memory is terrible right now and I can't remember exactly what it was. But this seems like something that should be tested in animal models first.

I covered the possibility of a "mucosal microbiota transplant" in my FMT roadmap proposal.

What I've noticed from my FMT's is that whatever effect I've experienced from the treatment has been the first to go when I've tried new experiments (diet changes, herbals etc.) and the old symptoms persists which I hypothesise is because the transplanted microbes only manages to colonize the top of the mucus layer and the old microbes live deeper down which gives them greater resilience.
I agree and I experience the same thing. One FMT donor can replace the effects of the previous donor, but both seem fairly superficial and easily lost. It's possible that a higher quality donor may have more permanent effects given that they seem to stimulate the immune system, but I haven't been able to test that.
 
I remember reading something on this topic but my memory is terrible right now and I can't remember exactly what it was. But this seems like something that should be tested in animal models first.

I covered the possibility of a "mucosal microbiota transplant" in my FMT roadmap proposal.


I agree and I experience the same thing. One FMT donor can replace the effects of the previous donor, but both seem fairly superficial and easily lost. It's possible that a higher quality donor may have more permanent effects given that they seem to stimulate the immune system, but I haven't been able to test that.
Yes high quality donors definitely matters a lot, but to wait for that one super donor who can cure all of our problems to finally show up, well that might just take an eternity...

Thanks for the write up in the other thread Mucosal microbiota transplant & clearing the gut mucosa prior to fmt
It got me thinking about NAC again and made me come up with a fourth alternative:

Use NAC AFTER FMT
NAC is sold as a supplement and is used by thousands of people, so using it on its own short term is at least considered safe. By using it some time after FMT (days, weeks?) maybe the change in viscosity from NAC will allow the new bacteria which have colonized the top layer of the mucosa to go deeper before the mucus solidifies again. Maybe this could give a better effect or longer lasting results for the FMT. Or maybe the antimicrobial properties of NAC will just hurt the new bacteria and weaken the effect of the transplant.

Since NAC and FMT are safe when used on their own, then maybe this is the safest alternative by separating them by time. This is all just in theory of course but I'm seriously considering to try it myself. I can't do another treatment right now for financial reasons though, so it's going to be some time before I'd be able to try it.

If anyone else would decide to do it before me, please do share your experience here.
 
Very interesting, this makes alot of sense. Ive come across some articles that cover other factors in the engraftment. This last time around I tried doing a bowel prep and a 48 hour fast so I’ll see how it goes.
 
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