Alterations in the microbiota have been observed in many human diseases, including
diseases of neurodegeneration. However, specific microbiome factors that either promote or
protect against neurodegeneration are largely unknown. We examined the effects of human
microbiota in tauopathies, a class of age-associated neurodegenerative diseases that are
characterized by the accumulation of tau protein inclusions. Using a Caenorhabditis elegans
model expressing an aggregate prone human tau protein, we examined the influence of specific
bacteria present in the human respiratory tract on neurodegeneration. We identified a
bacterial species, Rothia aeria, that is neuroprotective in a C. elegans model of tauopathy. We
determined that the R. aeria induced neuroprotection observed in PLM neurons is fat-3
dependent. fat-3 encodes the protein Delta (6)-fatty-acid desaturase. We also showed that a
lipid(s) produced by R. aeria decreases neurodegeneration in C. elegans. Further investigation is
needed to identify the lipid and the underlying mechanism. / Dissertation / Doctor of Philosophy (PhD) / The human body hosts trillions of microbes, including bacteria, viruses, and fungi. These
components make up the human microbiota. Gut microbiota have an essential role in human
health. In correlative studies, alterations in gut microbiota have been observed in many human
diseases and conditions, including Alzheimer’s disease (AD). Diet, antibiotics, and probiotics
change the composition of the microbiota and could decrease or increase the risk of developing
AD. Modulation of the microbiome through diet and other interventions could be beneficial for
AD. AD, the most common type of dementia, is a progressive brain disorder that slowly
destroys memory and mental skills. The Alzheimer’s Society of Canada estimates that over half
a million Canadians live with dementia, increasing significantly by 2031. The total estimated
indirect and direct costs of dementia in 2016 in Canada was $10.4 billion. Currently, no
treatments slow or stop Alzheimer’s disease and available medications can only improve the
symptoms in some patients.
One of the main characteristics of AD is the accumulation of a protein called tau in
neurons. In this research, we look at the impact of microbiota on AD using Caenorhabditis
elegans as a model organism. C. elegans is a free-living nematode. These nematodes are small,
transparent, feed on bacteria and have a simple nervous system. All these criteria make C.
elegans a perfect model for studying the impact of microbiota on AD. We exposed the C.
elegans model of AD with high tau aggregation in their neurons to different bacteria collected
from human microbiota and measured their neuronal health. We have found several species of
bacteria that decreased neurodegeneration in this model. Currently, we are investigating how these bacteria improve neuronal health. Our findings suggest the involvement of human
microbiota in AD. This suggests future treatment and preventative measures for AD should also
consider microbiota composition. The result of this research will expand our knowledge of AD
development and progression.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/29312 |
| Date | January 2023 |
| Creators | Mesbahi, Hiva |
| Contributors | MacNeil, Lesley, Biochemistry and Biomedical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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