Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Molecular Microbiology and Microbial Pathogenesis

Language

English (en)

Date of Award

5-24-2012

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Jeffrey Gordon

Abstract

The human gastrointestinal tract hosts trillions of microorganisms that impact human health. Although members of the domain Bacteria dominate our gut bioreactors, members of Archaea and Eukarya, and their viruses, are also represented. Methanobrevibacter smithii is the dominant Archaeon found in human gut, although only a subset of humans harbor this methanogen. Together with other hydrogen-consuming organisms: acetogens, sulfate reducing bacteria), M. smithii plays an important role in determining the efficiency of fermentation of dietary polysaccharides. Thus, deciphering the interactions between methanogens, acetogens and SRB and other members of the gut microbiota offers an important opportunity to gain new insights about how host energy balance is regulated, and new approaches for microbiome-directed attempts to control the partitioning of energy and nutrients from diet to host. This thesis addresses a number of basic questions: what forces determine if M. smithii is in a human gut microbiota; what other species in the gut microbial community co-occur with it; how does its genome evolve within an individual and between individuals within and between families. To address these questions, I used qPCR and 16S rRNA-directed pyrosequencing plus a variety of computational tools to examine the representation of M. smithii and SRB and other taxa in the fecal microbiota of healthy adult female monozygotic: MZ) and dizygotic: DZ) twin pairs, developed methods for isolating M. smithii from their frozen fecal samples, sequenced the genomes of 20 isolates recovered from two families, one composed of a MZ twin pair and the other of DZ twin pair, and characterized the isolates’ transcriptomes using RNA-Seq during in vitro growth under a variety of conditions. My studies revealed: i) carriage and levels of colonization correlate to a significant degree in MZ but not DZ twins,: ii) a core set of genes conserved between isolates;: iii) that based on variations in SNP and gene content/function, strains cluster according to individual host and then family, and: iv) suites of genes, including adhesin-like proteins, that are likely elements driving the evolutionary adaptation of this organism within and between human gut ecosystems. These results should help future efforts to develop strategies for manipulating the hydrogen economy of the gut in ways that promote health.

DOI

https://doi.org/10.7936/K7HD7SP5

Comments

Permanent URL: http://dx.doi.org/10.7936/K7HD7SP5

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