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

Spring 4-16-2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Jeffrey I Gordon

Abstract

The mammalian gut is residence to a large microbial community whose collective set of millions of genes: microbiome) encodes a vast array of functions, including many that process dietary components. Few tools are available to change the microbiome's properties to promote host health because the factors governing community assembly and operation are poorly understood. My thesis focused on the impact of one factor, host diet.

I used a variety of experimental and computational methods to perform a comparative metagenomic study of the fecal communities of 39 diverse mammals to assess microbiome variation. These animals included herbivores, omnivores and carnivores representing different portions of the mammalian tree, Targeted sequencing of the bacterial 16S rRNA gene and shotgun gene sequencing of total fecal DNA revealed that animals with similar diets possessed similar microbiomes, both in terms of bacterial species detected and the functions that their genomes encoded. A large number of genes were found in all gut microbiomes, but the relative abundance of many traits was differentially represented in carnivorous compared to herbivorous hosts, demonstrating that diet can shape a microbiome. We next studied microbiome variation within a single host species consuming a range of diets, using a population of 18 calorie-restricted adult humans with carefully recorded dietary intake. Even in these free-living, unrelated individuals, the amount of protein and dietary fiber consumed was significantly correlated with the variation in the gut metagenomes.

My second study addressed the period of dramatic dietary variation in human life when breast fed infants are weaned. The study population was a birth cohort of 103 children born in Bangladesh, some of who developed malnutrition during the first two years of life. My results demonstrate that despite large inter-personal variation, common patterns are found in the establishment of bacterial species and functions as the children age. The data revealed a developmental pattern of human gut microbiome functional assembly. This was exemplified by the emergence of glycan degradation capacity in all children studied. Some of the taxonomic and functional changes can be correlated with the host's diet, but many properties of the developing infant microbiome cannot be explained by diet alone.

DOI

https://doi.org/10.7936/K7GF0RHW

Comments

Permanent URL: http://dx.doi.org/10.7936/K7GF0RHW

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Microbiology Commons

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