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Cardiometabolic diseases, which include cardiovascular diseases and metabolic disorders such as obesity and diabetes, remain the leading cause of death worldwide.

In addition to various previously identified biomarkers, recent studies indicate a potential link between elevated trimethylamine N-oxide (TMAO) levels and the risk of cardiometabolic disease.

TMAO is a metabolic product of the human gut microbiome. Plasma TMAO levels increase with a high dietary intake of carnitine- and choline-containing products, such as red meat, eggs and intensively processed foods. Although almost all studies initially suggested negative effects of TMAO in cardiovascular and metabolic disease models, the changes induced by TMAO at the molecular level are still not completely clear. Moreover, recent studies reported protective effects that TMAO might have.


Image from Melita Ozola's doctoral thesis

The aim of the thesis was to investigate the TMAO-mediated effects on signalling pathways using experimental ex vivo and in vivo models of cardiometabolic diseases and identify potential strategies to regulate TMAO levels.

The study analysed the different effects of acute and long-term increase in TMAO concentrations.

The information presented in the abstract indicates that the role of TMAO in the pathogenesis of cardiometabolic diseases depends on the specific conditions, the disease model or organ system studied, and the duration of exposure.

Although there are conflicting results on the harmfulness of elevated TMAO levels, there is increasing interest in strategies to reduce TMAO levels, in particular by modulating the gut microbiome, which is an essential step in the biosynthesis pathways of TMAO. The results of this thesis provide evidence that both medications, such as antidiabetic drugs (metformin), and a specific dietary strategy, a fasting mimicking diet, can be effectively used to regulate TMAO levels.

Melita Ozola will defend her doctoral thesis Regulation of Trimethylamine N-oxide in Treatment of Cardiometabolic Diseases on 24 November 2023.
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