자료유형  

 학위논문

Control Number  

0017161619

International Standard Book Number  

9798382579863

Dewey Decimal Classification Number  

576

Main Entry-Personal Name  

Beller, Zachary Walter.

Publication, Distribution, etc. (Imprint  

[S.l.] : Washington University in St. Louis., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

241 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-11, Section: B.

General Note  

Includes supplementary digital materials.

General Note  

Advisor: Gordon, Jeffrey I.

Dissertation Note  

Thesis (Ph.D.)--Washington University in St. Louis, 2024.

Summary, Etc.  

요약Learning how members of the human gut microbiota compete and cooperate for dietary nutrients, such as fiber-associated glycans, should help facilitate development of more precise nutritional recommendations for improving health. To model how bacteria prioritize the utilization of different fiber glycans in the mammalian gut, germ-free mice were colonized with a 13-member consortium of cultured, genome-sequenced human bacterial strains, including seven Bacteroides species. Animals were fed a Western diet supplemented with pea fiber. Once the consortium had time to assemble, an inducible CRISPR-based system was used to deplete the absolute abundance of Bacteroides thetaiotaomicron or B. cellulosilyticus by 10- to 60-fold. Each type of knockdown resulted in specific, reproducible increases in the absolute abundances of other Bacteroides, with accompanying changes in their glycan prioritization, most notably involving changes in the expression of their polysaccharide utilization loci (PULs). The emergence of these 'alternate consumers' was associated with preservation of the community's capacity to metabolize fiber glycans, as judged by measurements of degradation of polysaccharides covalently attached to orally administered artificial food particles, and of monosaccharides and glycosidic linkages remaining in cecal contents. Finally, using a Cas9-PmCDA1 base editing system, we disrupted translation of transporters critical for utilizing abundant dietary polysaccharides in Bacteroides vulgatus, a B. cellulosilyticus knockdown-responsive taxon, to further characterize mechanisms associated with its increased fitness following knockdown. Using this approach to define how nutrient resource utilization is prioritized among community members could help delineate the origins of robustness and resiliency in the microbiota, as well as aid in the design of microbiota-directed therapeutics.

Subject Added Entry-Topical Term  

Microbiology.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Developmental biology.

Index Term-Uncontrolled  

Gnotobiotic mice

Index Term-Uncontrolled  

Human gut microbiome

Index Term-Uncontrolled  

Interbacterial interactions

Index Term-Uncontrolled  

Polysaccharide utilization

Added Entry-Corporate Name  

Washington University in St. Louis Biology & Biomedical Sciences (Computational & Systems Biology)

Host Item Entry  

Dissertations Abstracts International. 85-11B.

Electronic Location and Access  

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Control Number  

joongbu:657297