is this possible

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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is this possible

Postby juniords123 » Tue Jul 14, 2015 7:57 pm

hi just wanted to ask, if research found friendly gut bacteria that converts (foul smelling)TMA to (neautral smelling)TMAO,
and it was made into a probiotic yogurt which we can eat everyday, would this be a cure?????
because i read somewhere that they found skin flora(bacteria) that neautralised the TMAU smell.
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Re: is this possible

Postby FADworker » Mon Jul 27, 2015 4:29 pm

Good question. There are bacteria that can convert TMA to TMAO but, to be useful as a TMAuria therapeutic, they would need to be able to generate TMAO in the absence of oxygen (O2) and thrive within the human gut. Alternatively, it might be posible to introduce, via genetic engineering, the genes that mediate anaerobic TMA oxidation in the non gut-friendly bacteria into a more gut-friendly strain and use this GM strain in a probiotic form. However, even if any of this were possible the TMAO generated in the gut would likely be rapidly converted back (reduced) to TMA by other TMAO-reducatase-mediating strains resulting in a futile circular set of TMA>TMAO>TMA reactions. The human gut contains many 100s/1000s of different bacterial species each its own complicated bag of enzymes, etc capable of mediating many complex biochemical reactions.

It might be possible, however, to inhibit the formation of the TMA by bacteria in the gut by using drugs that block the enzymes that generate TMA from the intial dietary precursors, e.g., choline and carnitine. Gut bacterial enzymes that produce TMA from choline and carnitine have recently been identified. To be efficient, this approach would likely require a number of different drugs be taken each of which targets a different TMA-generating enzyme. Such an approach has been mooted recently as a result of the increasing number of positive associations reported between TMAO and diseases such as CVD (although I think the jury is still very much out as to the validity of any such association - it may well be associative but not causal. One wonders why asian, e.g. Japanese, populations who eat large amounts of TMAO-containing seafood are realtively free of CVD?). Another approach might be to use bacteriotherapy to replace a TMA-generating gut bacterial population with a different population of bacteria that has been depleted of species that contain such activites. I wrote a grant application to the UK Medical Research Council designed to attempt to identify whether differences in populations of such TMA-generating bacteria exist between TMAu patients and controls but it was unsuccessful.

Hope this answer helps.
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Re: is this possible

Postby PoetFire » Tue Jul 28, 2015 6:53 am

Hello Dr Dolphin

Re your grant request to the UK Medical Council, I wondered if the funding may possibly be raised via crowdfunding ?

Our community raised around $30,000+ for a NORD grant project a few years ago. I would guess if it was under say £50,000 it may be possible to crowdfund.
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