Arteriosclerosis Risk from TMA-forming Intestinal Bacteria

Systemic trimethylamine N-oxide (TMAO) is a key molecule in the pathogenesis of cardiovascular disease: it affects cholesterol and bile acid metabolism and promotes inflammation of the vessel wall. Intestinal bacteria form the precursor TMA from food, which liver enzymes rapidly oxidize to TMAO.

Our new diagnostic test,”Arteriosclerosis Risk Assessment”, detects the TMA-forming enzymes of the intestinal microbiota at the gene level and thus provides information on the plaque burden of the vessels by TMA from the intestine.

Studies on Atherogenic Effects

As early as 2013, physicians demonstrated a link between high TMAO plasma levels and cardiovascular events over the next three years. In another 2014 study, they looked at patients with heart failure. Compared to healthy control subjects, patients had elevated plasma TMAO levels. High TMAO levels (> 8.51 μM) were associated with significantly higher mortality than relatively low levels (<3.03 μM).

A recent clinical study has reaffirmed the atherogenic effects of TMAO by examining the relationships between TMAO levels and cardiovascular events in more than 2,000 patients from two different sources in Switzerland and the United States. The subjects had presented with suspicion of acute coronary syndrome. In both regions, TMAO levels were able to predict short-term and long-term risks of major cardiac complications. Overall, TMAO levels were higher in American patients than in Swiss patients, leading to more frequent complications among Americans.

Cholesterol Accumulation and Foam Cell Formation

Studies in mice on the causal relationships between TMA, TMAO and atherosclerosis have shown that the administration of choline or TMAO promotes foam cell formation in the arterial wall and the peritoneal cavity.
A TMAO, choline, or L-carnitine-containing diet also increased levels of scavenger receptors involved in cholesterol accumulation and foam cell formation. In the arterial wall, the liver and the intestine, the sterol metabolism changed.
In particular, the TMAO can also promote inflammation by activating pro-inflammatory proteins such as IL-6. Whether it hinders the healing of wounds, is still under discussion.