Potential new drug to inhibit microbial TMA production

Dr Dolphin was part of the team who first demonstrated that mutations in the FMO3 gene are the cause of the inherited (primary form) of TMAU.

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Potential new drug to inhibit microbial TMA production

Postby FADworker » Tue Dec 22, 2015 8:55 pm

Just though the Forum might be interested in a recent publication in Cell by Stanley Hazen's group at the Cleveland Clinic in which they report identification of a compound - dimethyl-butanol - capable of inhibiting the TMA-lyase responsible for TMA production from choline by gut microbes. They are interested in the possible therapeutic benefit for their posited relationship between TMAO and atherosclerosis but it should work for TMAu as well. Of course the compound would have to pass all the usual tox and regulatory checks, etc, etc and, in addition, be delivered successfully to the gut but it's a start.

http://www.sciencedirect.com/science/article/pii/S0092867415016293
http://www.sciencedirect.com/science/article/pii/S0092867415015743
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Re: Potential new drug to inhibit microbial TMA production

Postby Tenacity » Wed Jan 27, 2016 9:18 pm

Wouldn't it be amazing if this a) goes the distance and b) can be delivered safely to the target site? Just think, perfectly healthy, functioning little commensals doing all their commensally things, but not able to produce any TMA. No more antibiotics, no more restrictive diet, etc. Plus I quite like the idea of going all mother-earth on my gut flora. All these years of doing your thang without any regard for the inability of me, your host, to oxidise your by-products? Well, let's inhibit *your* enzymes for a bit, and see how *you* like it.

It's a shame their target group is atherosclerosis patients, as I'd totally have put my name down for phase II or III clinical trials, likelihood of being in the placebo group be darned.

Anyhoo, thanks for sharing! :)
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Re: Potential new drug to inhibit microbial TMA production

Postby PinkPanther » Thu Jan 28, 2016 1:26 pm

According to Wiki:

DMB is found in some balsamic vinegars, red wines, and some cold-pressed extra virgin olive oils and grapeseed oils.


I think I read somewhere else recently (MEBO site?) that extra virgin olive oil might be helpful, however, being a vegetarian I don't really consume much high choline food anyway. Hang on though, it might allow me to eat nuts, yay!
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Re: Potential new drug to inhibit microbial TMA production

Postby Tenacity » Thu Jan 28, 2016 7:30 pm

Oh yeah, I just saw that. How interesting. :D

My biomed knowledge is so patchy, though, I've no idea how four-chain alcohols are broken down in the body. I'm assuming DMB would get broken down by alcohol dehydrogenases in the stomach, the same as ethanol, and hence wouldn't reach the intestinal gut flora in one piece??

Um, red wine and balsamic vinegar enema, anybody??? :? :? :? :? :? :? :oops:
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Re: Potential new drug to inhibit microbial TMA production

Postby gemtree » Thu Feb 18, 2016 3:08 am

This looks great!
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