A water-soluble tomato extract rich in secondary plant metabolites lowers trimethylamine-n-oxide and modulates gut microbiota: a randomized, double-blind, placebo-controlled cross-over study in overweight and obese adults.

Background: Natural products rich in polyphenols have been shown to lower plasma trimethylamine-n-oxide (TMAO) known for its proatherogenic effects by modulating the intestinal microbiota.

Objectives: We aimed to determine the impact of Fruitflow, a water-soluble tomato extract, on TMAO, fecal microbiota, and plasma and fecal metabolites.

Methods: Overweight and obese adults (n = 22, BMI 28-35 kg/m) were included in a double-blind, placebo-controlled, cross-over study receiving 2×150 mg Fruitflow per day or placebo (maltodextrin) for 4 wk with a 6-week wash-out between interventions. Stool, blood, and urine samples were collected to assess changes in plasma TMAO (primary outcome) as well as fecal microbiota, fecal and plasma metabolites, and urine TMAO (secondary outcomes). In a subgroup (n = 9), postprandial TMAO was evaluated following a choline-rich breakfast (∼450 mg). Statistical methods included paired t-tests or Wilcoxon signed rank tests and permutational multivariate analysis of variance.

Results: Fruitflow, but not placebo, reduced fasting levels of plasma (-1.5 μM, P ≤ 0.05) and urine (-19.1 μM, P ≤ 0.01) TMAO as well as plasma lipopolysaccharides (-5.3 ng/mL, P ≤ 0.05) from baseline to the end of intervention. However, these changes were significant only for urine TMAO levels when comparing between the groups (P ≤ 0.05). Changes in microbial beta, but not alpha, diversity paralleled this with a significant difference in Jaccard distance-based Principal Component (P ≤ 0.05) as well as decreases in Bacteroides, Ruminococccus, and Hungatella and increases in Alistipes when comparing between and within groups (P ≤ 0.05, respectively). There were no between-group differences in SCFAs and bile acids (BAs) in both faces and plasma but several changes within groups such as an increase in fecal cholic acid or plasma pyruvate with Fruitflow (P ≤ 0.05, respectively). An untargeted metabolomic analysis revealed TMAO as the most discriminant plasma metabolite between groups (P ≤ 0.05).

Conclusions: Our results support earlier findings that polyphenol-rich extracts can lower plasma TMAO in overweight and obese adults related to gut microbiota modulation. This trial was registered at clinicaltrials.gov as NCT04160481 (https://clinicaltrials.gov/ct2/show/NCT04160481?term= Fruitflow&draw= 2&rank= 2).