The role of microbiota metabolites in post-antibiotic nutrient acquisition by Clostridium difficile

Placeholder Show Content

Abstract/Contents

Abstract
Clostridium difficile is the most common cause of infectious antibiotic associated diarrhea, however the mechanisms underlying its ability to expand after antibiotics have not yet been described. Understanding how a dysbiotic gut microbiota is able to promote C. difficile, and conversely, how a healthy gut microbial community inhibits C. difficile are of great interest. The work in this thesis has led to an understanding of the instrumental roles that the microbiota plays in C. difficile gut colonization using gnotobiotic and conventional mouse models. Chapter 1 contains a review describing what is known about the important functions of the gut microbiota and its contribution to pathogenesis. In Chapter 2, we demonstrate that C. difficile and Salmonella typhimurium both utilize microbiota-liberated host sugars to expand upon antibiotic-treatment. In Chapter 3, we reveal other expansion strategies used by C. difficile and highlight the use of a microbiota-derived metabolite succinate by C. difficile to expand after perturbations. Chapter 4 contains three collaborative projects including two novel treatments for C. difficile-associated diseases, a prebiotic and a toxin inhibitor, as well as a new model used to study C. difficile-microbiota interactions. Finally Chapter 5 describes future considerations for this work and the field. These studies have revealed the basic mechanisms employed by C. difficile to expand upon antibiotic treatment and identified novel treatment strategies for C. difficile-associated diseases.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2014
Issuance monographic
Language English

Creators/Contributors

Associated with Ferreyra, Jessica Ann
Associated with Stanford University, Department of Microbiology and Immunology.
Primary advisor Sonnenburg, Justin, 1973-
Thesis advisor Sonnenburg, Justin, 1973-
Thesis advisor Monack, Denise M
Thesis advisor Relman, David A
Thesis advisor Sherlock, Gavin
Advisor Monack, Denise M
Advisor Relman, David A
Advisor Sherlock, Gavin

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Jessica Ann Ferreyra.
Note Submitted to the Department of Microbiology and Immunology.
Thesis Thesis (Ph.D.)--Stanford University, 2014.
Location electronic resource

Access conditions

Copyright
© 2014 by Jessica Ann Ferreyra
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

Also listed in

Loading usage metrics...