Kasahara Kazuyuki, Kerby Robert L, Cross Tzu-Wen L, Everhart Jessica, Kay Colin, Bolling Bradley W, Bäckhed Fredrik, Rey Federico E
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Res Sq. 2023 Jan 10:rs.3.rs-2431147. doi: 10.21203/rs.3.rs-2431147/v1.
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) () 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) 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.
膳食类黄酮的肠道细菌代谢会产生多种酚酸，但其对健康的作用仍知之甚少。在此，我们表明，补充常见的类黄酮槲皮素会影响肠道微生物群组成，并使喂食高微生物可利用碳水化合物（MAC）饮食的传统饲养（ConvR）载脂蛋白E（）基因敲除（KO）小鼠的动脉粥样硬化负担显著降低。然而，在食用低水平MAC的特定饮食的动物中未观察到这种效果。此外，我们发现槲皮素对动脉粥样硬化的影响需要肠道微生物，因为向食用高MAC饮食的无菌（GF）载脂蛋白E KO小鼠补充这种类黄酮不会影响动脉粥样硬化的发展。代谢组学分析显示，在食用高MAC饮食的ConvR小鼠中，摄入槲皮素会显著提高血浆中苯甲酰谷氨酸和原儿茶酸的水平，而在GF小鼠或食用添加了该类黄酮的低MAC饮食的传统动物中未观察到这些升高。此外，这些代谢物的水平与动脉粥样硬化负担呈负相关。总之，这些结果表明，槲皮素对动脉粥样硬化的有益作用受肠道微生物和膳食MAC的影响。
