There is a huge opportunity for further research in the gut-heart axis. Gut microbiome strategies have emerged for the prevention of cardiovascular disease due to TMAO being dependent on metabolism by the intestinal microbiota. Here we show how natural products rich in polyphenols lower plasma trimethylamine n-oxide (TMAO) known for its proatherogenic effects by modulating the intestinal microbiota. In this study, Fruitflow®, a water soluble tomato concentrate, rich in secondary metabolites, including nucleosides, phenolic conjugates and polyphenols was to be investigated to see how this substrate could be utilized by the host microorganism. A randomized double blind, placebo controlled crossover study comprising of 37 overweight participants was undertaken.