The role of the gut microbiota in the function and integrity of brain barriers
type: CreativeWork
description: The barriers of the brain help maintain an optimal environment for central nervous system (CNS) function and homeostasis. There are many instances such as during age related disorders and neuropsychiatric disorders in which these barriers are under threat. Importantly, the gut-microbiota can interact with the brain barriers, thereby altering barrier physiology and communication with the brain. This bidirectional communication is known as the microbiota-gut-brain axis. Modulation of the gut microbiota can thereby alter functions in the brain, potentially through influence of the brain barriers. In this thesis we focus on the interface of both brain barriers; the blood-cerebrospinal fluid barrier (CSF) and blood-brain barrier (BBB) in microbiota-gut-brain axis communication. In particular, using germ-free mice which lack a gut microbiota, we investigated the contributing role of the gut microbiota in regulation of the blood-CSF barrier. Following confocal microscopy for visualization of the tight junction protein, ZO-1, germ-free mice were found to have a disruption of the tight junction protein networks in isolated choroid plexus tissue. Similar assessment of the choroid plexus capillaries revealed no difference between germ-free and conventional mice. Since microbial metabolites are some of the known contributing factors of the gut microbiota’s manipulation of the barriers, we next investigated the effects of physiological concentrations of short chain fatty acids (SCFAs), butyrate and propionate, with and without induced barrier dysfunction (LPS) on the actin cytoskeleton and tight junction protein dynamics using an in vitro BBB model. We found that the butyrate and propionate altered filamentous actin directionality, increased tight junction protein spikes, and protected from LPS induced decrease in mitochondrial footprint and barrier integrity measured by trans-endothelial electrical resistance (TEER). While we do not yet understand the dynamics of the BBB follow…
abstract: The barriers of the brain help maintain an optimal environment for central nervous system (CNS) function and homeostasis. There are many instances such as during age related disorders and neuropsychiatric disorders in which these barriers are under threat. Importantly, the gut-microbiota can interact with the brain barriers, thereby altering barrier physiology and communication with the brain. This bidirectional communication is known as the microbiota-gut-brain axis. Modulation of the gut microbiota can thereby alter functions in the brain, potentially through influence of the brain barriers. In this thesis we focus on the interface of both brain barriers; the blood-cerebrospinal fluid barrier (CSF) and blood-brain barrier (BBB) in microbiota-gut-brain axis communication. In particular, using germ-free mice which lack a gut microbiota, we investigated the contributing role of the gut microbiota in regulation of the blood-CSF barrier. Following confocal microscopy for visualization of the tight junction protein, ZO-1, germ-free mice were found to have a disruption of the tight junction protein networks in isolated choroid plexus tissue. Similar assessment of the choroid plexus capillaries revealed no difference between germ-free and conventional mice. Since microbial metabolites are some of the known contributing factors of the gut microbiota’s manipulation of the barriers, we next investigated the effects of physiological concentrations of short chain fatty acids (SCFAs), butyrate and propionate, with and without induced barrier dysfunction (LPS) on the actin cytoskeleton and tight junction protein dynamics using an in vitro BBB model. We found that the butyrate and propionate altered filamentous actin directionality, increased tight junction protein spikes, and protected from LPS induced decrease in mitochondrial footprint and barrier integrity measured by trans-endothelial electrical resistance (TEER). While we do not yet understand the dynamics of the BBB follow…
author: Knox, Emily G.
language: en
keywords: Blood brain barrier, Gut microbiota, Microbial metabolites, Blood CSF barrier, Choroid plexus
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
date published: 2023
date modified: 2026-07-24T01:46:32Z
provider: University College Cork
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University College Cork

PropertyValue
property ID: Handle
value: https://hdl.handle.net/10468/15966