News & Views on Systemic Body Odor and Halitosis such as trimethylaminuria TMAU. If you have fecal odors or bowel odors it may be metabolic/systemic

Showing posts with label stool dna. Show all posts
Showing posts with label stool dna. Show all posts

25 October 2016

Bacteroidetes don't produce trimethylamine from choline

 2012 paper suggests bacteroidetes phyla are poor at degrading choline to trimethylamine.
Firmicutes, Actinobacteria, and Proteobacteria can produce TMA.
Ubiome suggest Firmicutes make up 60% of normal flora, Bacteroidetes 30%.
My own Ubiome results average (of 4) were Firmicutes 70%, Bacteroidetes 26%.
My own opinion, not enough known of the gut flora for me to have an opinion.
This post more a 'for your information' post, rather than any 'breakthrough'.
Perhaps others should try stool DNA testing.

The new Phillips/Shephard TMAU-FMO3 overview paper mentioned a 2012 paper which they seemed to have great credence for. The research in the paper proved TMA could be produced from choline by certain gut bacteria flora phyla (Firmicutes, Actinobacteria, and Proteobacteria) but not from Bacteroidetes.

Quote from Phillips/Shephard/Fennema paper

Free choline is absorbed throughout the small intestine and is subsequently integrated into cell membranes or actively taken up by the liver, where it can be converted to betaine, phosphocholine, or lecithin (Zeisel, 1990). High amounts of choline may exceed the absorptive capacity and pass through to the large intestine, however, where it is metabolized to methylamines by microbial action (Zeisel et al., 1983). Choline is a quaternary ammonium compound containing a trimethylammonium moiety. Thus, it can act as a precursor for TMA (Zeisel et al., 1989; Chalmers et al., 2006). The bacterial conversion of choline to TMA involves the cleavage of the carbon-nitrogen bond of choline, producing TMA and acetaldehyde (Hayward and Stadtman, 1959). Craciun and Balskus (2012) proposed that a glycyl radical enzyme CutC (EC 4.3.99.4), encoded by the bacterial choline utilization gene cluster (cut), might act as a choline TMA-lyase to catalyze this initial step in choline degradation (Fig. 1). This was confirmed by demonstrating that deletion of cutC in Desulfovibrio desulfuricans abolished the ability of the organism to produce TMA from choline. Bioinformatics analysis revealed cutC homologs in 89 bacterial genomes. The homologs are not distributed evenly among the major bacterial phyla of the human gut, being present in Firmicutes, Actinobacteria, and Proteobacteria spp. but absent from Bacteroidetes (Craciun and Balskus, 2012). Table 1 shows bacteria known to be associated with formation of TMA via choline degradation.

This is the paper they refer to :
Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme

Firmicutes and Bacteroidetes seem to make up the bulk of the gut flora. There seems to be different opinions on what that % make-up should be for a healthy gut.

Ubiome suggest the healthy gut should have about 70% Firmicutes and 30% Bacteroidetes.

My own Firmicute/Bacteroidetes ratio :
I have tested with Ubiome 4 times.
In 3 samples my Firmicute was slightly higher than normal. Bacteroidetes was slightly lower.

My view on the knowledge of the human gut flora :
I would suggest if you compare it to the history of USA, it may be around the year 1620. Perhaps I'm wrong, but my impression is so little is understood of the gut flora (Oct 16). I'm hoping technology has caught up and we will be at around year 1900 in the next few years.

My view on my own results :
I will not be excitedly trying to alter my firmicute/bacteriodetes ratio, though may look around for info. It seems that bacteroidetes are not the type usually put in 'probiotics'. Possibly partly as they are so 'sensitive' (and die easy in oxygen). Possibly there is no 'bacteroidetes' probiotic on the market. The general view seems to be taking 'prebiotics' is the best hope of feeding bacteroidetes.

Perhaps others can do the stool DNA test :
Since the stool  DNA test is relatively cheap, and sometimes they do special offers (e.g. 3 for 1), perhaps others with systemic body odor/halitosis can do the test and mention anything they want about the results in the comment section of this post.

Stool DNA test suppliers :
Ubiome (choose citizen science)
American Gut (also 'UK Gut')

These are the 2 best known suppliers. Thankfully, they are consumer health friendly, and not health learning obstacles as is the case with normal DNA tests, urine tests etc. The spirit of the testing would be that it may be not very useful, but perhaps will be in hindsight.    

What's this to do with systemic body odor ?
My own view is that most cases of SBO are probably due to enzyme weaknesses, probably the bulk of which are due to sub-par FMO3 enzyme function. But I also think gut dysbiosis will be a common factor in 'FMO3 body odor', probably as part of the syndrome, and perhaps often the 'tipping point'.

Currently TMAU is the only acccepted form of systemic body odor. My own view is that 'FMO3 body odor' can mean smelling of any FMO3 substrate rather than just TMA, and many of the volatiles produced in the gut are probably FMO substrates. Although this paper was about TMA, perhaps bacteroidetes can't produce other FMO3 substrates, but who knows.

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30 July 2016

Paper : firmicutes produce more TMA than bacteroides

New paper :
The aim seems to be to see how trimethylamine precursors (choline in foods etc) affect TMA-oxide levels in a group of healthy young men. The conclusion seems to be that those with a higher ratio of Firmicutes / Bacteroide gut bacteria generate more trimethylamine from precursors.    

The paper was done with the 2011 Hazen et al TMA-oxide - Heart Disease theory in mind, which links TMA-oxide with blood vessel damage.

Research paper :
Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: a randomized controlled trial
Cornell University

What's this to do with systemic body odor ?
My own current opinion is that most cases of systemic/metabolic body odor are probably to do with FMO3 enzyme and it's substrates. Most cases are probably an FMO3 weakness that means overload of FMO3 substrates at any time. The volatiles produced by gut bacteria are probably often FMO3 substrates. Currently the only volatile accepted as causing systemic/metabolic body odor is trimethylamine. With the interest in TMA-oxide since 2011, it's likely a TMA blocker will be a therapy. 

My opinion :
My 2 main points are :

1. This seems to be a one-off research paper. From a lab with no previous history on TMA-oxide. Cornell is greatly respected but I don't know how significant or accepted the result will be.

2. I feel there is too little known about the gut flora overall. Both in knowledge and in testing. So for me I can take or leave the info. It may someday prove to be important, but for now I don't know.

My Ubiome stool DNA results :
Previously I wrote how my Ubiome Stool DNA result was lower than average in firmicutes. For now I wouldn't take this as my norm. As I say, I think not enough is known about the gut flora for me to think anything. So I won't be making any changes due to this result. I'm waiting for the Procter & Gamble TMA-blocker to come to market.

Summary :
It's too speculative for me to make any conclusions from this at the moment. I will keep a lookout though.

Other Links :
Cornell in-house article on TMAO (4Aug16)

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3 March 2016

2nd batch ubiome results : fecal body odor

This is my 2nd batch of my Ubiome microbiome dna results.
I don't see anything that may be a biomarker for 'fecal body odor'.
But I don't know how to interpret the results.
And also the technology and understanding of the microbiome is at an early stage.
I still think microbiome testing is worthwhile (as it's so cheap)

2nd batch of Ubiome results :
I tested before in 2014. This new batch of 3 was part of their Xmas offer '3 for price of 1'. I have only briefly looked at the results.

Note :
These are just 4 examples of the data given in Ubiome results.

Fecal Body Odor / FMO3 malodor
I reckon FBO is caused by FMO3 substrates, so I tend to look out for anything to do with FMO3 substrates in the results.

FBO and dysbiosis :
I think gut dysbiosis goes naturally with 'Fecal Body Odor' (a syndrome). My question is  :
Do people with FBO have a particular gut dysbiosis ? or
Do those with FBO have general gut dysbiosis ?
This is where I think microbiome testing will be very useful, but perhaps the understanding is at too early a stage.

My interp of my results :
I can't make much of it.

Of initial interest is :
Secondary metabolite biosynthesis.
Flavone and flavonol biosynthesis 0.7X
Flavonoid biosynthesis

I mention these 2 as they were low and the word 'flavone' is maybe associated with Vitamin B2 and/or flavin enzymes ? Maybe not.

Closing remarks :
Next time I might try using 'American Gut' purely as they are a different lab.
I suggest doing these tests even though they currently may not give us any relevant info, mainly as they are the right way to go and they are cheap.
Sometimes Ubiome do special offers 3 for 1 etc.

What do I think causes 'Fecal Body Odor' :
I think the smells are probably mostly sulfides, and some amines, of a certain structure (soft nucloephilic) that are probably naturally oxidized mainly by FMO3 enzyme.
My theory is :
The person will have a weakness of some % of the FMO3 enzyme
They will tend to a certain or common gut dysbiosis, exacerbating the problem due to overload.

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23 September 2014

My Ubiome results for fecal body odor

I did the Ubiome microbiome DNA test to see if it would give any clues to what may cause my metabolic body odor which expresses itself as bowel malodors, including fecal and gas and other malodors. My guess is that most of the malodors are caused by sulfides and amines created in the gut by the gut flora.  I have a theory that it may be a syndrome, and 'gut dysbiosis' may be part of the syndrome. Either a type of gut dysbiosis specific to metabolic bowel malodors, or a general gut dysbiosis.

I note that the Ubiome test only tests for bacteria, so will not notice fungus such as candida, or parasites.

I don't see anything much noticeable about my results that may give any clues, but I am not an expert and have only glance at the results. Perhaps in isolation they don't mean as much as they would if grouped with other 'metabolic malodor' sufferers.

My own current remarks about my results :
Lactobacillus and Bifidobacteria were much lower than the average sample
Bacteroidetes were more than averageDesulfibrivio speiec were much lower than normal (I thought this might be a culprit in 'fecal body odor'. Not ruling it out yet)

Below are more screenshots of my results. There is more details than shown in these photos. :

Notes about my graphs :
The way to judge the horizontal graphs is :
vertical black line : that's my result
vertical blue line : that's the average
orange area in line strips : I guess that means if my black line is in there then it's 'very abnormal'  

Each page here shows just the top 5 of each category. There are actually about 15 in each list.

On reflection, it seems a lot of my 'good bacteria' are much lower than normal, even though the 'very good' bacteria in a normal person make up a small % of the total microbes.

A lot of the microbes do not have any explanation yet, so I can't interpret what their result means

Overall I cannot make any conclusions yet, due to lack of knowledge and lack of info.

But I am glad I tested as it's all there currently is and retrospectively it may be vcry useful.    



So far I can't make any conclusions over my results, but hopefully over time they will be of use retrospectively or compared to other metabolic malodor results.

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survey still OPEN

TMA blocker pill (links)

P&G - Cleveland press release aug 2015
1st mention of 'DMB pill' dec 2015
FMO3 DNA testing
Update Aug 17 :
Genos is back with it's EXOME test
link

Note :
Exome/Genome testing may be better option than single gene testing.

See this post : link

Note : Genos Exome Testing.

Exome testing is almost the same price now as single gene testing. Also Genos is consumer friendly, which standard DNA labs are not.

So the blog offer to test solely for FMO3 is almost obsolete, and so no longer offered.


Does Genos fully sequence FMO3 gene ?

At the moment it is not clear, but hoped this will become clear over the next few months

Note : possible 'wild west' way of testing FMO3
Use an ancestry dna site and rummage through the raw data

TMAU Webinar #5 : Preti et al