Xanthohumol Requires the Intestinal Microbiota to Improve Glucose Metabolism in Diet-Induced Obese Mice.
Xanthohumol Requires the Intestinal Microbiota to Improve Glucose Metabolism in Diet-Induced Obese Mice.
复制标题
DOI：
10.1002/mnfr.202100389
复制
发表时间：
2021-11
影响因子：
5.2
通讯作者：
Gombart AF
中科院分区：
文献类型：
--
作者：
Logan IE;Shulzhenko N;Sharpton TJ;Bobe G;Liu K;Nuss S;Jones ML;Miranda CL;Vasquez-Perez S;Pennington JM;Leonard SW;Choi J;Wu W;Gurung M;Kim JP;Lowry MB;Morgun A;Maier CS;Stevens JF;Gombart AF
多酚黄腐酚（XN）改善饮食诱导的肥胖动物模型中的功能失调的葡萄糖和脂质代谢。由于XN改变了肠道微生物群的组成，我们假设XN需要微生物群来介导其益处。为了验证我们的假设，我们给常规和无菌雄性瑞士韦伯斯特小鼠喂食低脂饮食（10%脂肪来源的热量）、高脂饮食（60%脂肪来源的热量）或高脂饮食，并以60 mg/kg体重/天的剂量补充XN，持续10周，并测量葡萄糖和脂质代谢参数。在常规小鼠中，我们发现XN补充剂降低了血浆胰岛素浓度并改善了胰岛素抵抗的稳态模型评估。在无菌小鼠中，XN补充剂未能改善这些结果。粪便样本16 S rRNA基因测序分析表明，XN补充剂改变了微生物组成，并显著改变了肠道微生物群的预测功能能力。此外，肠道微生物群将XN代谢成生物活性化合物，包括二羟蒽腐酚，一种具有改善的生物利用度的抗肥胖化合物。XN需要肠道微生物群来介导其益处，这涉及复杂的饮食-宿主-微生物群相互作用，以及微生物组成和功能能力的变化。我们的研究结果保证了未来的宏基因组研究，这将为复杂的微生物-微生物相互作用和饮食-宿主-微生物群相互作用提供深入了解。在小鼠模型中，黄腐酚--一种在啤酒花中发现的天然化合物--改善了健康状况，改变了肠道微生物的组成。由于黄腐酚改变了肠道微生物的组成，我们假设这些微生物是必需的，以便看到饮食中补充黄腐酚的益处。因此，我们使用我们最近开发的瑞士韦伯斯特小鼠模型来测试饮食中添加黄腐酚的效果，使用传统（有肠道微生物的小鼠）和无菌（没有肠道微生物的小鼠）-瑞士韦伯斯特小鼠。我们在10周的时间内给这些小鼠喂食低卡路里、高卡路里或补充黄腐酚的高卡路里饮食。我们发现，只有传统的小鼠受益于黄腐酚补充剂，以改善葡萄糖代谢的形式。我们发现，黄腐酚的补充增加了三种细菌的相对丰度，特别是嗜粘蛋白阿克曼氏菌，Parabacteroides goldsteinii和Alistipes finegoldii。我们发现支持这三种微生物的证据部分负责介导与黄腐酚补充剂相关的益处。然而，我们不能排除肠道微生物群落作为一个整体的作用。
The polyphenol xanthohumol (XN) improves dysfunctional glucose and lipid metabolism in diet-induced obesity animal models. Because XN changes intestinal microbiota composition, we hypothesized that XN requires the microbiota to mediate its benefits. To test our hypothesis, we fed conventional and germ-free male Swiss Webster mice either a low-fat diet (10% fat derived calories), a high-fat diet (60% fat derived calories), or a high-fat diet supplemented with XN at 60 mg/kg body weight per day for 10 weeks, and measured parameters of glucose and lipid metabolism. In conventional mice, we discovered XN supplementation decreased plasma insulin concentrations and improved Homeostatic Model Assessment of Insulin Resistance. In germ-free mice, XN supplementation failed to improve these outcomes. Fecal sample 16S rRNA gene sequencing analysis suggested XN supplementation changes microbial composition and dramatically alters the predicted functional capacity of the intestinal microbiota. Furthermore, the intestinal microbiota metabolizes XN into bioactive compounds, including dihydroxanthohumol, an anti-obesogenic compound with improved bioavailability. XN requires the intestinal microbiota to mediate its benefits, which involves complex diet-host-microbiota interactions with changes in both microbial composition and functional capacity. Our results warrant future metagenomic studies, which will provide insight into complex microbe-microbe interactions, and diet-host-microbiota interactions. In mouse models, xanthohumol – a natural compound found in hops – improves health and changes the composition of the gut microbes. Because xanthohumol changes gut microbial composition, we hypothesized these microbes are required in order to see the benefits of xanthohumol supplementation of the diet. Therefore, we used our recently developed Swiss Webster mouse model to test the effects of xanthohumol supplementation of the diet using both conventional – those who have gut microbes – and germ-free – those without gut microbes – Swiss Webster mice. We fed these mice either a diet low in calories, high in calories, or the high calorie diet supplemented with xanthohumol over a period of 10 weeks. We found that only the conventional mice benefitted from xanthohumol supplementation, in the form of improved glucose metabolism. We found that xanthohumol supplementation increased the relative abundance of three bacteria in particular, Akkermansia muciniphila, Parabacteroides goldsteinii, and Alistipes finegoldii. We found evidence that supports these three microbes are partially responsible for mediating the benefits associated with xanthohumol supplementation. However, we cannot rule out a role for the community of gut microbes as a whole.
登录
查看更多内容
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
29.4
作者：
Bouter, Kristien E.;van Raalte, Daniel H.;Nieuwdorp, Max
通讯作者：
Nieuwdorp, Max
DOI：
10.1073/pnas.1219451110
发表时间：
2013-05-28
影响因子：
11.1
作者：
Everard, Amandine;Belzer, Clara;Cani, Patrice D.
通讯作者：
Cani, Patrice D.
影响因子：
3.1
作者：
Fukizawa, Shinya;Yamashita, Mai;Murayama, Norihito
通讯作者：
Murayama, Norihito
影响因子：
5
作者：
Chen, Jia-Xing;Deng, Chao-Yin;Yang, Dong-Hui
通讯作者：
Yang, Dong-Hui