Gut Microbiota Plays a Central Role to Modulate the Plasma and Fecal Metabolomes in Response to Angiotensin II
Gut Microbiota Plays a Central Role to Modulate the Plasma and Fecal Metabolomes in Response to Angiotensin II
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DOI：
10.1161/hypertensionaha.119.13155
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发表时间：
2019-07-01
期刊：
影响因子：
8.3
通讯作者：
Pluznick, Jennifer L.
中科院分区：
文献类型：
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作者：
Cheema, Muhammad Umar;Pluznick, Jennifer L.
肠道微生物代谢物与血压调节有关；然而，迄今为止，只有少数微生物代谢物被研究过。在这项研究中，我们假设对慢性血管紧张素II输注模型中肠道微生物代谢物的变化进行无偏筛选将识别与血压调节相关的新型微生物代谢物。为了做到这一点，我们使用了常规和无菌小鼠，它们被植入了微型泵，注入生理盐水或Ang II。我们的目的是鉴定在常规小鼠中被angii治疗改变的代谢物，而在无菌小鼠中则没有，这表明它们依赖于肠道微生物群。血浆和粪便样品均采用液相色谱-串联质谱法进行处理和分析。在血浆中，我们发现4种代谢物显著上调，8种代谢物显著下调。在无菌小鼠中，这些代谢物都没有变化。同样，在常规小鼠的粪便中，我们发现了25种代谢物显着上调，71种代谢物显着下调。在无菌小鼠中，这些代谢物都没有变化。最后，粪便16S测序显示，接受Ang II治疗的常规小鼠的微生物组发生了显著变化，包括性别特异性变化。这些数据表明，受angii差异调节的代谢物依赖于肠道微生物群。
Gut microbial metabolites have been implicated in contributing to blood pressure regulation; however, only a few microbial metabolites have been examined to date. In this study, we hypothesized that an unbiased screen for changes in gut microbial metabolites in a chronic Ang II (angiotensin II) infusion model would identify novel microbial metabolites associated with blood pressure regulation. To accomplish this, we used both conventional and germ-free mice, which had been implanted with minipumps to infuse either saline or Ang II. Our aim was to identify metabolites that were altered with Ang II treatment in conventional mice, but not in germ-free mice, indicating that they are dependent on the gut microbiota. Both plasma and feces samples were processed and analyzed using liquid chromatography-tandem mass spectroscopy. In plasma, we identified 4 metabolites that were significantly upregulated and 8 metabolites that were significantly downregulated with Ang II treatment in conventional mice; none of these metabolites changed in germ-free mice. Similarly, in feces, we identified 25 metabolites that were significantly upregulated and 71 metabolites that were significantly downregulated with Ang II treatment in conventional mice; none of these metabolites changed in germ-free mice. Finally, fecal 16S sequencing revealed significant shifts in the microbiome of conventional mice with Ang II treatment, including sex-specific changes. These data demonstrate that the metabolites that are differentially regulated with Ang II are dependent on the gut microbiome.