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Functional genomic examinations of interactions between common members of the human gut microbiota.

机译：人体肠道菌群常见成员之间相互作用的功能基因组学检查。

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摘要

The adult human gut microbiota consists of hundreds to thousands of bacterial species, the majority belonging to the Bacteroidetes and the Firmicutes. Differences in the balance between these phyla has been linked to obesity in mice and humans. However, little is known about their interactions in vivo . I have used comparative and functional genomics, proteomics and biochemical assays to identify the ways they marshal their genomic resources to adapt to life together in the distal gut.I first annotated the complete genome sequences of two human gut Bacteroidetes (Bacteroides vulgatus and Parabacteroides distasonis ) and two Firmicutes (Eubacterium rectale and E. eligens). By comparing the genomes of all sequenced gut Bacteroidetes and Firmicutes, I found that gut Bacteroidetes' genomes contain large groups of genes responsible for (i) sensing, binding, and metabolizing the varied polysaccharides that they encounter in the distal intestine and (ii) constructing their polysaccharide capsules. These portions of their genomes have been shaped by lateral gene transfer, including phage and conjugative transposons, as well as by gene duplication. By colonizing germ-free mice with B. thetaiotaomicron, or B. vulgatus, or both species together, I documented that B. vulgatus upregulates its unique glycan-degrading enzymes to adapt to the presence of B. thetaiotaomicron.In contrast to the Bacteroidetes, the Firmicutes have smaller genomes, a significantly smaller proportion of glycan-degrading genes, and are suited to degrade a more specialized assortment of dietary carbohydrates. By colonizing germ-free mice with E. rectale and/or B. thetaiotaomicron , I showed that B. thetaiotaomicron, like B. vulgatus, upregulates its unique glycoside hydrolase activities to adapt to the presence of E. rectale, increasing its degradation of host-derived glycans that E. rectale cannot use. In contrast, E. rectale downregulates its polysaccharide degradation genes and upregulates nutrient transporters, likely allowing it to access sugars released by B. thetaiotaomicron's glycoside hydrolases. These models of the human gut microbiota illustrate niche specialization and functional redundancy within the Bacteroidetes, the adaptable niche specialization that likely underlies the success of Firmicutes in this habitat, and the importance of host glycans as a nutrient foundation that ensures ecosystem stability.
机译：成年人类肠道菌群由成百上千种细菌组成，大多数属于拟杆菌属和硬菌属。这些门之间的平衡差异与小鼠和人类的肥胖有关。然而，关于它们在体内的相互作用知之甚少。我使用比较和功能性的基因组学，蛋白质组学和生化分析方法来确定他们调配基因组资源以适应远端肠道中的生活的方式。我首先注释了两种人类肠道拟杆菌（Bacteroides vulgatus和Parabacteroidoids distasonis）的完整基因组序列。和两个Firmicutes（真细菌和E. eligens）。通过比较所有测序的肠道拟杆菌和Firmicutes的基因组，我发现肠道拟杆菌的基因组包含大量基因，这些基因负责（i）感知，结合和代谢它们在远端肠中遇到的各种多糖，以及（ii）构建他们的多糖胶囊。它们的基因组的这些部分已通过侧向基因转移（包括噬菌体和结合性转座子）以及通过基因复制而形成。通过用B. thetaiotaomicron或B. vulgatus或这两个物种一起对无菌小鼠进行定殖，我证明了B. vulgatus上调了其独特的聚糖降解酶以适应B. thetaiotaomicron的存在。 Firmicutes的基因组较小，聚糖降解基因的比例明显较小，并且适合降解更特殊的饮食碳水化合物。通过用无菌的大肠杆菌和/或嗜热芽孢杆菌B. thetaiotaomicron定植无菌小鼠，我表明，嗜盐芽孢杆菌B. thetaiotaomicron像B. vulgatus一样，上调了其独特的糖苷水解酶活性，以适应直肠的大肠杆菌的存在，从而增加了宿主的降解大肠埃希氏菌不能使用的衍生聚糖。相比之下，大肠埃希氏菌下调其多糖降解基因并上调营养物转运蛋白，这可能使它能够获得由Thetaiotaomicron的糖苷水解酶释放的糖。这些人类肠道菌群模型阐明了拟杆菌中的生态位专长和功能冗余，适应性的生态位专长可能是该生境中Firmicutes成功的基础，以及宿主聚糖作为确保生态系统稳定的营养基础的重要性。

著录项

  • 作者

    Mahowald, Michael Anthony.;

  • 作者单位

    Washington University in St. Louis.;

  • 授予单位 Washington University in St. Louis.;
  • 学科 Biology Ecology.Biology Genetics.Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 286 p.
  • 总页数 286
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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