TMA the inflammation baddie ? TMAO a goodie ??

2 big FMO3-smell related stories recently :

1 : new study : TMA is the inflammation baddie and not TMAO ???

2. small Messina Italy lab looking at whether FMO3 common haplotypes with ma currently regarded harmless etc may affect FMO3 function in combination (readers say yes ??)

This post will look at the 'TMA-bad' recent study by Quadram Institute, Norwich, England

Note : paper details not fully absorbed. post may have errors.

Theory of paper :  in mice models, TMA caused blood-brain barrier inflammation, whereas TMAO was protective !!

This seems to contradict the TMAO-CVD theory put forward by Cleveland Clinic scientists in 2011.

That said, they are looking at at the blood-brain barrier, whereas Cleveland's theory is about blood vessel internal damage (blood vessels to heart etc). So both could be right (???). 

This paper seems to have been funded by an Alzheimers charity.

Group behind the study :

Quadram Institute UK is based around microbiome research etc. Seems to be quite well funded, probably by Government.

Microbiome research seems to have given us little useful info up until now. Possibly this is still the way their research is going.

Tweets same to suggest it was a 'eureka' wild research guess from a scientist based there.

The online fecal body odor forums are probably decades ahead of them in this type of study thinking. 

The idea for the study seems to be of Profs Lesley Hoyles and Simon McArthur.

How will this affect FMO3-smelly people ?

Probably win-win either way. Whether its TMA or TMAO they try to block, doesn't matter as they will both likely block TMA. For TMA to be the baddie would be preferable, as it means it's the main target for big pharmas, but TMAO as a target likely means blocking TMA anyway.

In theory it means TMA people are meant to be more prone to CVD etc, but 1 opinion is neither TMA or TMAO are much important re CVD but pharma-fanaticism about TMA/TMAO is very welcome. Perhaps TMA makes more sense, but who knows about either. Maybe TMA is just a sign of dysbiosis.

Details on the paper :

Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide

Lesley Hoyles, Matthew G. Pontifex, Ildefonso Rodriguez-Ramiro, M. Areeb Anis-Alavi, Khadija S. Jelane, Tom Snelling, Egle Solito, Sonia Fonseca, Ana L. Carvalho, Simon R. Carding, Michael Müller, Robert C. Glen, David Vauzour & Simon McArthur 

https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-021-01181-z

 

"Here, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner."

Accompanying video. pic.twitter.com/kxkrcKQue0

— Professor Lesley Hoyles (@BugsInYourGuts) November 27, 2021

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