A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice
A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice
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DOI：
10.1038/ismej.2013.89
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发表时间：
2013-10-01
期刊：
影响因子：
11
通讯作者：
Sonnenburg, J. L.
中科院分区：
文献类型：
--
作者：
Marcobal, A.;Kashyap, P. C.;Sonnenburg, J. L.
由于微生物组中预测的基因数量众多，对群落动态和群落-宿主相互作用的了解相对较少，因此确定宿主相关微生物生态系统的功能状态具有挑战性。代谢组学方法，其中大量的小分子代谢物可以在生物样品中被定义，提供了一个有前途的途径“指纹”微生物群的功能状态。在这里，我们使用优化的超高效液相色谱-质谱法检测了人类肠道微生物群对人源化（HUM）小鼠粪便和尿液代谢组的影响。HUM与常规小鼠尿液和粪便代谢组学谱之间的差异支持微生物群代谢组学贡献的宿主特异性方面，与不同的微生物组成一致。用不同人类供体人源化的小鼠的微生物群组成和代谢组的比较显示，在供体样品中观察到的绝大多数代谢组学特征在相应的HUM小鼠中产生，并且个体特异性特征表明功能的“个性化”方面可以在小鼠中重建。给小鼠喂食定义的定制饮食导致代谢物特征的改变，这表明宿主饮食提供了改变肠道微生物群功能的途径，而这反过来又可以通过代谢组学进行监测。使用由一个或两个物种组成的定义的模型微生物群，我们表明，简化的社区可以驱动主机代谢谱的重大变化。我们的研究结果表明，代谢组学构成了肠道微生物群及其与宿主相互作用的功能表征的强大途径。
Defining the functional status of host-associated microbial ecosystems has proven challenging owing to the vast number of predicted genes within the microbiome and relatively poor understanding of community dynamics and community-host interaction. Metabolomic approaches, in which a large number of small molecule metabolites can be defined in a biological sample, offer a promising avenue to 'fingerprint' microbiota functional status. Here, we examined the effects of the human gut microbiota on the fecal and urinary metabolome of a humanized (HUM) mouse using an optimized ultra performance liquid chromatography-mass spectrometry-based method. Differences between HUM and conventional mouse urine and fecal metabolomic profiles support host-specific aspects of the microbiota's metabolomic contribution, consistent with distinct microbial compositions. Comparison of microbiota composition and metabolome of mice humanized with different human donors revealed that the vast majority of metabolomic features observed in donor samples are produced in the corresponding HUM mice, and individual-specific features suggest 'personalized' aspects of functionality can be reconstituted in mice. Feeding the mice a defined, custom diet resulted in modification of the metabolite signatures, illustrating that host diet provides an avenue for altering gut microbiota functionality, which in turn can be monitored via metabolomics. Using a defined model microbiota consisting of one or two species, we show that simplified communities can drive major changes in the host metabolomic profile. Our results demonstrate that metabolomics constitutes a powerful avenue for functional characterization of the intestinal microbiota and its interaction with the host.