Bidirectional Interactions Between the Gut Microbiome and Nervous System

Author: Griffiths, Jessica Anne

Year: 2024

Degree: Dissertation (Ph.D.)

Advisor: Mazmanian, Sarkis K.

Committee Members: Gradinaru, Viviana; Lois, Carlos; Lester, Henry A.; Mazmanian, Sarkis K.

Option: Bioengineering

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.

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