Functional Genomic Examinations Of Interactions Between Common Members Of The Human Gut Microbiota

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 <italic>(Bacteroides vulgatus</italic> and <italic>Parabacteroides distasonis)</italic> and two Firmicutes <italic>(Eubacterium rectale</italic> and <italic>E. eligens).</italic> 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 <italic>B. thetaiotaomicron,</italic> or <italic>B. vulgatus,</italic> or both species together, I documented that <italic>B. vulgatus</italic> upregulates its unique glycan-degrading enzymes to adapt to the presence of <italic>B. thetaiotaomicron.</italic> 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 <italic>E. rectale</italic> and/or <italic>B. thetaiotaomicron,</italic> I showed that <italic>B. thetaiotaomicron,</italic> like <italic>B. vulgatus,</italic> upregulates its unique glycoside hydrolase activities to adapt to the presence of <italic>E. rectale,</italic> increasing its degradation of host-derived glycans that <italic>E. rectale</italic> cannot use. In contrast, <italic>E. rectale</italic> downregulates its polysaccharide degradation genes and upregulates nutrient transporters, likely allowing it to access sugars released by <italic>B. thetaiotaomicron's</italic> 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.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biology and Biomedical Sciences: Molecular Microbiology and Microbial Pathogenesis

Year dc:date.available

2010

Author dc:creator

• Mahowald, Michael

Contributors dc:contributor

• Jeffrey Gordon

• Biology
• Microbiology
• Genetics
• Ecology
• bacteria
• commensalism
• genomics
• gut

Language dc:language

English (en)

DOI

https://doi.org/10.7936/K7FN1470

OAI identifier oai:identifier

oai:openscholarship.wustl.edu:etd-1221