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Gut microbiome and diet
By Professor Elizabeth Shephard, PhD
For MEBO Annual Meetup and Conference 2017
The Betsy South Beach, Miami Beach
March 31, 2017, 8:00 p.m.
Slide #2 GUT MICROBIOME:
- The term microbiome refers to a collection of bacteria that inhabit a particular niche in our body, and we have a number of these microbiomes.
- ~90% of an adult human is bacterial.
- 10x more bacterial cells than human cells.
Slide #3 PRIMARY TMAU – FMO3, DIET AND MICROBIOME:Why is the gut microbiome relevant to Primary Trimethylaminuria?
- When we eat food, gut microbial action in the gut breaks down the bond of the Trimethylamine group, by liberating nitrogen, methyl group, and other atoms that might be linked to them, and liberate the molecule resulting in trimethylamine (TMA).
- This [odorous] trimethylamine (TMA) molecule is very quickly absorbed [into the bloodstream] and is taken to the liver.
- In the liver we have this enzyme called FMO3, which is able to catalyze a reaction, which adds an oxygen (the O here in the diagram) onto the nitrogen (N) to form the molecule called trimethylaminuria-N-Oxide (TMAO) [non-odorous], which is then were very rapidly excreted through the kidneys.
- And so, the cause of trimethylaminuria [TMAU1] is when the FMO3 gene carries a mutation, such that the enzyme that is encoded by this gene, cannot carry out this reaction very efficiently.
- Flavin containing Monooxygenase 3 is the metabolic enzyme in the liver that adds the oxygen atom (O) to trimethylamine (TMA) to make it non-odorous.
Slide #4 MULTIPLE MICROBIOME-MEDIATED PATHWAYS CAN LEAD TO TMA PRODUCTION
- A gut free of bacteria does not produce TMA.
- Several bacterial phyla produce TMA.
- In the gut we have many different pathways that can be carried out by different bacteria to produce trimethylamine (TMA).
- Bacteria can actually convert trimethylamine (TMA) [odorous] into trimethylamine-N-Oxide [non odorous], and use it themselves. So this would be by bacterial enzyme.
Slide #5 FISH DIET:There are a number of different constituents of the diet that have been shown when you culture bacteria to be able to give rise to trimethylamine. These include choline, betaine, carnitine, and also trimethylamine n-oxide (TMAO) [from fish and seafood] itself.
- Marine fish that live in the sea or in deep fresh water lakes are the richest dietary source of TMA because to protect their protein from breaking down in salt water and pressure changes, the fish Flavin Containing monooxygenase enzyme (protein) is increased to produce a lot of TMAO, which protects their proteins in the muscles of the fish from breaking down.
- In humans eating fish (high in TMAO) our gut bacteria converts it to TMA with our gut bacteria’s TMAO reductase enzyme and the bacteria uses the TMA for itself. The rest of the TMA is passed from the gut to the liver to be metabolized by the FMO3 metabolic enzyme to add an oxygen atom to make it TMAO (non-odorous).
Slide #6 How do we actually measure the content of a particular foodstuff?
- The two methods [of measuring the content of TMA in foods], chemical digestion and biological digestion, don't always give the same answer. One is a very harsh chemical condition, and the other one is reliant on the biological digestion of the foodstuffs in the gut by the bacteria that reside in the gut of that Individual.
- So just looking at a table doesn't necessarily give you the amount of trimethylamine (TMA) that's might be released when a human eats this particular foodstuff.
Slides #7 and #8 TABLES OF DIETARY SOURCES of TMA:Lists TMA content of foods, including fruits, vegetables, and chicken, mushroom, pork, egg, beef, soya, lamb, mackerel, and cod, indicating significant differences between chemical digestion and biological digestion.
Slide #9 DIETARY INDOLES INHIBIT FMO3 ACTIVITY:Researchers identified an inhibitor of FMO3 activity in brussel sprouts.
We are most grateful to Professor Elizabeth Shephard, PhD, for her continual monumental support through the years to the MEBO Mission by educating us through her three PowerPoint presentations, by working with United States and United Kingdom governmental agencies and councils, and by spearheading MRC funded research into a therapeutic for TMAU.
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