Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance.

Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance.
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DOI:
10.1080/19490976.2021.1940791
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发表时间:
2021-01
期刊:
影响因子:
12.2
通讯作者:
Weir TL
Weir TL
中科院分区:
医学2区
文献类型:
--
作者:
Trikha SRJ;Lee DM;Ecton KE;Wrigley SD;Vazquez AR;Litwin NS;Thomas KN;Wei Y;Battson ML;Johnson SA;Kuhn KA;Colgan SP;Gentile CL;Weir TL

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最近的临床前数据表明,肠道微生物群的改变可能是将肥胖与血管功能障碍(心血管疾病的早期征兆)联系起来的一个重要因素。本研究的目的是通过检查人类血管表型是否可以通过肠道微生物群传播来开始转化这些临床前数据。我们假设,与接受来自瘦人肠道微生物群的无菌小鼠相比,来自肥胖个体肠道微生物群的无菌小鼠会表现出血管功能减弱。我们将血管功能不同的肥胖和瘦弱年龄和性别匹配参与者的粪便移植到无菌小鼠体内。使用主成分分析,定植小鼠的微生物群按照第一主成分按供体组分离,占数据集中总变异性的 70-93%。接受瘦个体移植的小鼠的微生物群的特征还包括α多样性增加,以及潜在有益细菌的相对丰度增加,包括双歧杆菌、乳杆菌和卵形拟杆菌。相对于接受瘦素供体微生物群或保持无菌状态的小鼠,接受肥胖供体微生物群的小鼠的内皮依赖性扩张、主动脉脉搏波速度和葡萄糖耐量显着改变。这些数据表明,在没有体重或饮食控制差异的情况下,与肥胖相关的人类肠道微生物群足以改变无菌小鼠的血管表型,并为未来的临床试验提供依据,以测试微生物群靶向疗法在预防或治疗心血管疾病方面的功效。
Recent preclinical data suggest that alterations in the gut microbiota may be an important factor linking obesity to vascular dysfunction, an early sign of cardiovascular disease. The purpose of this study was to begin translation of these preclinical data by examining whether vascular phenotypes in humans are transmissible through the gut microbiota. We hypothesized that germ-free mice colonized with gut microbiota from obese individuals would display diminished vascular function compared to germ-free mice receiving microbiota from lean individuals. We transplanted fecal material from obese and lean age-and sex-matched participants with disparate vascular function to germ-free mice. Using Principle Component Analysis, the microbiota of colonized mice separated by donor group along the first principle component, accounting for between 70–93% of the total variability in the dataset. The microbiota of mice receiving transplants from lean individuals was also characterized by increased alpha diversity, as well as increased relative abundance of potentially beneficial bacteria, including Bifidobacterium, Lactobacillus, and Bacteroides ovatis. Endothelium-dependent dilation, aortic pulse wave velocity and glucose tolerance were significantly altered in mice receiving microbiota from the obese donor relative to those receiving microbiota from the lean donor or those remaining germ-free. These data indicate that the obesity-associated human gut microbiota is sufficient to alter the vascular phenotype in germ-free mice in the absence of differences in body weight or dietary manipulation, and provide justification for future clinical trials to test the efficacy of microbiota-targeted therapies in the prevention or treatment of cardiovascular disease.
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