
doi: 10.7936/k7k935j0
The human gut harbors tens of trillions of microbes belonging to all three domains of life, Bacteria, Archaea, and Eukarya; most are members of Bacteria. These organisms collaborate and compete for functional niches and physical space: habitats), together forming a continuously functioning metabolic organ that influences many aspects of host biology. The factors that drive the assembly, determine the stability, and shape the adaptive responses of the gut microbiota to a variety of perturbations are the subject of intense study as greater appreciation is gained of the importance of this microbial community for human health. My thesis focused on the viral component of the microbiota that had been less characterized than its bacterial component. I first developed and applied a series of experimental and computational tools for metagenomic analyses of viruses purified from frozen fecal samples obtained from healthy adult monozygotic twin pairs and their mothers living in the USA, over the course of a year. The virome in this population was dominated by phages and exhibited high inter-personal variation and contrasting intrapersonal stability, suggesting a prevalent temperate lifestyle rather than a predator-prey relationship that is a feature of marine microbial communities. To further characterize the role of phage in shaping gut community structure, I colonized adult germ-free mice with a defined model human gut microbiota composed of 15 sequenced human gut symbionts, seven of which harbored 10 prophages, one of which: Bacteroides cellulosilyticusWH2) was represented by a library of >25,000 isogenic transposon mutants covering 80% of genes in its genome. Once assembled, this model microbiota was subjected to a staged phage attack with a pool of virus-like particles: VLPs) purified from the fecal microbiota of five humans from the first study. Shotgun sequencing of DNA isolated from the input human VLP preparation, cecal and fecal samples collected over time from these gnotobiotic mice, and VLPs recovered from ...
Virome, Microbial communities, Metagenomics, Biology, Human gut microbiota
Virome, Microbial communities, Metagenomics, Biology, Human gut microbiota
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