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Gut Microbiome Modulates Microglia Physiology in Homeostatic and Disease States


Abdel-Haq, Reem (2022) Gut Microbiome Modulates Microglia Physiology in Homeostatic and Disease States. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/ht1j-2461.


The gastrointestinal tract (GI) harbors a complex community of ~100 trillion bacteria, fungi, and viruses collectively referred to as the gut microbiome. Through direct and indirect signaling mechanisms, the gut microbiome exerts its effects on almost every organ system, including the brain. Constant, bi-directional communication along the gut-brain axis is required for the normal and healthy development of the host Central Nervous System (CNS). One of the cells in the CNS shaped by microbial-derived cues is microglia, the resident immune cells in the brain. Aberrant microglia activity is a driving force of several neurological diseases in which the gut microbiome plays a role, including Parkinson’s disease (PD). In this thesis, we explore the interplay between gut microbiota signaling and microglia physiology during homeostatic and disease states. We first detail how microbial signaling along the gut-brain axis shapes microglial development and function. Next, we explore how the gut microbiome composition influences microglial activation states in the context of disease. Leveraging a preclinical mouse model of PD, we show that dietary-driven changes to the gut microbiome through the use of prebiotics attenuates motor deficits and α-synuclein aggregation. These effects result from changes in microglial gene expression and activation status. Collectively, these findings have broad implications for the gut microbiome research community and highlight potential for development of microbiome-based therapies for diseases of the brain.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Gut Microbiome, Neuroscience, Nervous System, Microglia, Parkinson's Disease, Gut-Brain-Axis
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Mazmanian, Sarkis K.
Thesis Committee:
  • Gradinaru, Viviana (chair)
  • Mazmanian, Sarkis K.
  • Thomson, Matthew
  • Chan, David C.
Defense Date:20 May 2022
Funding AgencyGrant Number
Department of DefensePD160030
Aligning Science Across Parkinson's (ASAP)ASAP-000375
Heritage Medical Research InstituteHMRI-15-09-01
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
Record Number:CaltechTHESIS:03162022-173632582
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for ch. 2 ItemArticle in Nature: Microbiota regulate social behaviour via stress response neurons in the brain ItemArticle in Developmental Biology: Maintaining multipotent trunk neural crest stem cells as self-renewing crestospheres ItemArticle in Caltech Letters: Trust your gut: the body's second brain
Abdel-Haq, Reem0000-0002-7418-5736
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14517
Deposited By: Reem Abdel-Haq
Deposited On:27 May 2022 15:25
Last Modified:03 Jun 2022 16:13

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