Restriction lift date: 2034-03-31
Microbial regulation of barrier function in the gut-brain axis
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Date
2023
Authors
Sánchez Díaz, Paula
Journal Title
Journal ISSN
Volume Title
Publisher
University College Cork
Published Version
Abstract
The gut microbiome plays a critical role in host health through modulation of gut
and blood-brain barrier integrity, responding to factors such as diet, stress, and
medication. A key pathway by which the gut microbiota affects gut and bloodbrain
barrier integrity is through the production of bioactive metabolites. This
thesis explores the role of barriers in the microbiota-gut-brain axis, which are
essential for the proper functioning of body systems and homeostasis. Chapter 2
investigates how fermenting infant nutrient formulations with different
bifidobacteria strains isolated from infant gut microbiome can influence the
integrity of gut and blood-brain barriers in vitro. The study found that the presence
of bifidobacteria strains, in some cases, had protective effects on the barriers, and
these effects sometimes differed depending on the barrier studied. Chapter 3
explores the effects of indole and two of its derivates, indole-3-acetate and indole-
3-propionate, on gut barrier function in vitro. The results indicate that indole has
a protective effect on barrier function, particularly at higher concentrations, and
indole-3-acetate has a protective effect at the lowest concentrations tested.
Surprisingly, indole-3-propionate was not protective and at higher concentrations
exacerbated the effects of LPS-induced disruption. Finally, Chapter 4 focuses on
the effect of cancer therapy, specifically cisplatin, on gut and blood-brain barrier
structure in mice, to further explore the role of gut microbiome in cancer-related
cognitive impairment. The study used mice treated with cisplatin to investigate
the expression of genes involved in the structural function of barriers and
inflammation, as well as gene expression of receptors activated by microbial
ligands in the ileum, colon, and hippocampus. The results showed that cisplatin
affected gene expression in a region- and dose-dependent manner, leading to
changes in anxiety-like and fatigue behaviours in mice. Overall, this research
highlights the critical role of the gut microbiome in gut barrier and blood-brain
barrier function. Microbial metabolite supplementation may present a useful
therapeutic option for disease processes involving disruption of the gut and/or
blood-brain barriers.
Description
Keywords
Barrier , Microbiome , Indole , Blood-brain barrier , Gut barrier
Citation
Sanchez Diaz, P. 2023. Microbial regulation of barrier function in the gut-brain axis. MSc Thesis, University College Cork.