Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing
Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing
复制标题
DOI：
10.1073/pnas.1219247110
复制
发表时间：
2013-03-19
影响因子：
11.1
通讯作者：
Wagner, Michael
中科院分区：
文献类型：
--
作者：
Berry, David;Stecher, Baerbel;Wagner, Michael
动物和人类的肠道粘膜分泌一系列化合物，在宿主组织和肠道内容物之间建立物理屏障，这一分离对健康至关重要。一些致病微生物以及共生肠道微生物区系的成员已被证明能够分解这些分泌的化合物。由于在活体内研究复杂的肠道生态系统的困难，我们对共生微生物区系对宿主化合物的降解的了解仅限于关于简化模型系统的知识。在这项研究中，我们引入了一种克服以前技术限制的方法，使我们能够观察肠道中的哪些微生物细胞使用宿主衍生的化合物。我们加入了稳定同位素标记的苏氨酸静脉注射。并结合荧光原位杂交和高分辨率二次离子质谱仪成像，以表征单个细菌细胞对宿主蛋白的利用。我们发现两种细菌是体内重要的寄主-蛋白质觅食者，即嗜酸拟杆菌和粘液阿克曼氏菌。使用诺生菌小鼠，我们证明了微生物区系组成决定了这些生物觅食的大小和模式，证明了一个复杂的微生物区系是必要的，以便充分利用这一利基。这些结果强调了肠道微生物区系体内研究的重要性，本研究提出的方法将是解决动物和人类微生物组研究中许多其他关键问题的有力工具。
The animal and human intestinal mucosa secretes an assortment of compounds to establish a physical barrier between the host tissue and intestinal contents, a separation that is vital for health. Some pathogenic microorganisms as well as members of the commensal intestinal microbiota have been shown to be able to break down these secreted compounds. Our understanding of host-compound degradation by the commensal microbiota has been limited to knowledge about simplified model systems because of the difficulty in studying the complex intestinal ecosystem in vivo. In this study, we introduce an approach that overcomes previous technical limitations and allows us to observe which microbial cells in the intestine use host-derived compounds. We added stable isotope-labeled threonine i.v. to mice and combined fluorescence in situ hybridization with high-resolution secondary ion mass spectrometry imaging to characterize utilization of host proteins by individual bacterial cells. We show that two bacterial species, Bacteroides acidifaciens and Akkermansia muciniphila, are important host-protein foragers in vivo. Using gnotobiotic mice we show that microbiota composition determines the magnitude and pattern of foraging by these organisms, demonstrating that a complex microbiota is necessary in order for this niche to be fully exploited. These results underscore the importance of in vivo studies of intestinal microbiota, and the approach presented in this study will be a powerful tool to address many other key questions in animal and human microbiome research.