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Bidirectional Interactions Between the Gut Microbiome and Nervous System

Citation

Griffiths, Jessica Anne (2024) Bidirectional Interactions Between the Gut Microbiome and Nervous System. Dissertation (Ph.D.), California Institute of Technology. https://resolver.caltech.edu/CaltechTHESIS:02042024-025331192

Abstract

There is roughly one microbe for every human cell in your body. Though some are inconsequential hitchhikers, and some are potentially harmful, many perform beneficial roles. This thesis focuses on the function and interaction of resident microbes within laboratory mice, with the hope that it may translate to us as humans. Chapter (1) highlights recent findings of microbiome involvement in neurologic disorders. Each subsequent chapter presents a different interaction between the mammalian nervous system and gut microbiome. (2) Excitatory signaling in the brain is partially regulated by a genetic factor (Shank3), which is further modulated by environmental interactions through presence or absence of the gut microbiome. This genetic factor implicated in brain and behavior also affects gastrointestinal function and inflammation susceptibility. (3) Applying powerful genetic tools developed for the brain to the enteric nervous system reveals the impact of different enteric neuron populations on gut motility and fluid secretion as well as the immune system, pancreatic activity, and microbial populations. (4) Common opinion has shifted from the belief that microbes are primarily pathogens to viewing them as symbiotic organisms. With this paradigm shift, the artificially clean laboratory mouse microbiome has been found to stunt the immune system, and is being reevaluated. Male mice with natural “wild” microbiomes have altered behavioral and neurological profiles, which may reflect a more physiological state.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:gut, microbiome, microbiota, gut-brain axis, enteric nervous system, autism, neurodevelopment, mouse behavior
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Bioengineering
Thesis Availability:Not set
Research Advisor(s):
  • Mazmanian, Sarkis K.
Thesis Committee:
  • Gradinaru, Viviana (chair)
  • Lois, Carlos
  • Lester, Henry A.
  • Mazmanian, Sarkis K.
Defense Date:25 January 2024
Non-Caltech Author Email:jessica.griffiths481 (AT) gmail.com
Funders:
Funding AgencyGrant Number
Aligning Science Across Parkinson's (ASAP)ASAP-000375
Aligning Science Across Parkinson's (ASAP)ASAP-020495
Michael J. Fox FoundationUNSPECIFIED
Caltech Center for Environmental and Microbial InteractionsUNSPECIFIED
National institutes of Health (NIH)T32GM007616
Record Number:CaltechTHESIS:02042024-025331192
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:02042024-025331192
Related URLs:
URLURL TypeDescription
https://doi.org/10.1186/s13073-018-0609-3DOIArticle adapted for chapter 1
https://doi.org/10.1101/2021.04.12.439539DOIArticle adapted for chapter 2
ORCID:
AuthorORCID
Griffiths, Jessica Anne0000-0002-5586-1567
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:16285
Collection:CaltechTHESIS
Deposited By: Jessica Griffiths
Deposited On:14 Feb 2024 23:30
Last Modified:14 Feb 2024 23:37

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