Trimethylamine N-oxide

TMAO (trimethylamine N-oxide) is a gut microbiome metabolite formed from choline, lecithin and L-carnitine by certain gut bacteria. The liver enzyme FMO3 oxidises the bacterial TMA into TMAO in the blood. TMAO is looked at in cardiovascular diagnostics alongside the lipid values. The value depends on the gut bacteria, the intake of the precursors, the activity of the liver enzyme FMO3 and excretion via the kidneys.

What TMAO does in the body

TMAO is formed in two steps between the gut and the liver. Certain gut bacteria split choline – free or from phosphatidylcholine (lecithin) –, betaine and L-carnitine with their own enzymes such as choline TMA lyase, releasing trimethylamine (TMA); carnitine is partly converted via the intermediate gamma-butyrobetaine. TMA is absorbed from the gut and reaches the liver via the portal vein, where the enzyme FMO3 oxidises it into TMAO. Sea fish also contains TMAO directly. TMAO is excreted mostly unchanged via the kidneys. In cell and animal studies, TMAO influenced reverse cholesterol transport and bile acid formation, the uptake of cholesterol into scavenger cells and the excitability of platelets.

Low TMAO – what happens in the body?

A low value shows that little TMA is being formed or that it is excreted quickly – for example when the gut flora contains only few TMA-producing bacteria, after antibiotic treatment or with a low intake of the precursors. A low value then has no pathological significance of its own. An exception is reduced activity of the liver enzyme FMO3, usually inherited: TMA is then hardly converted into TMAO, accumulates and is released through sweat, breath and urine. This leads to a fishy body odour (trimethylaminuria), while TMAO itself stays low.

High TMAO – what happens in the body?

A high value arises when the gut bacteria form a lot of TMA, when many precursors or sea fish were taken in shortly before the measurement, or when the kidneys excrete TMAO less well – reduced kidney function makes the value rise markedly. In experimental studies, TMAO promoted the uptake of cholesterol into scavenger cells of the vessel wall, made platelets easier to activate, strengthened inflammatory signals in the inner vessel wall and reduced the removal of cholesterol via bile acids. In observational studies, higher TMAO values were associated with cardiovascular disease. How far TMAO acts itself or mainly reflects kidney function and the gut flora has not yet been conclusively clarified.

The interpretation is given in your report.