Gut microbiota and diet matrix modulate the effects of the flavonoid quercetin on atherosclerosis.

Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted in a significant reduction in atherosclerosis burden in conventionally-raised (ConvR) Apolipoprotein E (ApoE) knockout (KO) mice fed a high-MAC (microbiota-accessible carbohydrates) diet. However, this effect was not observed in animals consuming a defined diet containing low levels of MAC. Furthermore, we found that the effect of quercetin on atherosclerosis required gut microbes, as supplementation of this flavonoid to germ-free (GF) ApoE KO mice consuming the high-MAC diet did not affect the development of atherosclerosis. Metabolomic analysis revealed that consumption of quercetin significantly increased plasma levels of benzoylglutamic acid and protocatechuic acid in ConvR mice exposed to the high-MAC diet, while these increases were not observed in GF mice or conventional animals consuming the low-MAC diet supplemented with the flavonoid. Furthermore, levels of these metabolites were negatively associated with atherosclerosis burden. Altogether, these results suggest that the beneficial effects of quercetin on atherosclerosis are influenced by gut microbes and dietary MAC.

Contribution of Berry Polyphenols to the Human Metabolome.

Diets rich in berries provide health benefits, however, the contribution of berry phytochemicals to the human metabolome is largely unknown. The present study aimed to establish the impact of berry phytochemicals on the human metabolome. A "systematic review strategy" was utilized to characterize the phytochemical composition of the berries most commonly consumed in the USA; (poly)phenols, primarily anthocyanins, comprised the majority of reported plant secondary metabolites. A reference standard library and tandem mass spectrometry (MS/MS) quantitative metabolomics methodology were developed and applied to serum/plasma samples from a blueberry and a strawberry intervention, revealing a diversity of benzoic, cinnamic, phenylacetic, 3-(phenyl)propanoic and hippuric acids, and benzyldehydes. 3-Phenylpropanoic, 2-hydroxybenzoic, and hippuric acid were highly abundant (mean > 1 µM). Few metabolites at concentrations above 100 nM changed significantly in either intervention. Significant intervention effects (P < 0.05) were observed for plasma/serum 2-hydroxybenzoic acid and hippuric acid in the blueberry intervention, and for 3-methoxyphenylacetic acid and 4-hydroxyphenylacetic acid in the strawberry intervention. However, significant within-group effects for change from baseline were prevalent, suggesting that high inter-individual variability precluded significant treatment effects. Berry consumption in general appears to cause a fluctuation in the pools of small molecule metabolites already present at baseline, rather than the appearance of unique berry-derived metabolites, which likely reflects the ubiquitous nature of (poly)phenols in the background diet.