Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
Wisconsin Institute for Discovery, Madison, WI, USA.
Nat Microbiol. 2018 Dec;3(12):1461-1471. doi: 10.1038/s41564-018-0272-x. Epub 2018 Nov 5.
Humans with metabolic and inflammatory diseases frequently harbour lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Here we show that a prominent gut-associated butyrate-producing bacterial genus (Roseburia) is inversely correlated with atherosclerotic lesion development in a genetically diverse mouse population. We use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary plant polysaccharides to: impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization; lower systemic inflammation; and ameliorate atherosclerosis. Furthermore, intestinal administration of butyrate reduces endotoxaemia and atherosclerosis development. Together, our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis.
患有代谢和炎症性疾病的人类肠道中通常含有较低水平的产生丁酸盐的细菌。然而，目前尚不清楚这些生物体水平的变化是否与疾病的发展有关，以及饮食是否会改变这些细菌对健康的影响。在这里，我们表明，在一个遗传多样化的小鼠群体中，一种与肠道相关的主要的丁酸盐产生细菌属（Roseburia）与动脉粥样硬化病变的发展呈负相关。我们使用定植有不同产生丁酸盐能力的合成微生物群落的无菌载脂蛋白 E 缺陷型小鼠来证明肠道罗斯伯里氏菌与膳食植物多糖相互作用：影响肠道中的基因表达，使代谢从糖酵解转向脂肪酸利用；降低全身炎症；并改善动脉粥样硬化。此外，肠道内给予丁酸盐可降低内毒素血症和动脉粥样硬化的发展。总之，我们的结果说明了可改变的饮食-微生物相互作用如何影响心血管疾病，并表明旨在增加产生丁酸盐的细菌的代表性可能为预防动脉粥样硬化提供保护。
