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Bidirectional Interactions Between the Gut Microbiome and Nervous System


Griffiths, Jessica Anne (2024) Bidirectional Interactions Between the Gut Microbiome and Nervous System. Dissertation (Ph.D.), California Institute of Technology.


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:Public (worldwide access)
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)
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:
Related URLs:
URLURL TypeDescription adapted for chapter 1 adapted for chapter 2
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
Deposited By: Jessica Griffiths
Deposited On:14 Feb 2024 23:30
Last Modified:12 Jun 2024 20:58

Thesis Files

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