Altered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy

Tau is a microtubule-associated protein that stabilizes the neuronal cytoskeleton. In the family of neurodegenerative diseases known as tauopathies, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), and chronic traumatic encephalopathy (CTE), abnormal tau aggregation destabilizes mi...

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Autores principales:	Jerrik Rydbom, Halea Kohl, Vanesa R. Hyde, Kelly M. Lohr
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tau Drosophila gut microbiome motility antimicrobial peptide (AMPs) innate immune activation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/2bd58d18ae3a4258b87a2935558ce5b4
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spelling	oai:doaj.org-article:2bd58d18ae3a4258b87a2935558ce5b42021-11-03T16:51:45ZAltered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy1662-453X10.3389/fnins.2021.731602https://doaj.org/article/2bd58d18ae3a4258b87a2935558ce5b42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.731602/fullhttps://doaj.org/toc/1662-453XTau is a microtubule-associated protein that stabilizes the neuronal cytoskeleton. In the family of neurodegenerative diseases known as tauopathies, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), and chronic traumatic encephalopathy (CTE), abnormal tau aggregation destabilizes microtubule structure, contributing to a cascade of cellular processes leading to neuronal cell death. The gut microbiome has increasingly become a target of neurodegenerative disease research since gut microbiome imbalances have been linked to protein aggregation and inflammation through a bidirectional axis linking the gut and brain. Accordingly, the present study examined tau-mediated changes to gut microbiome composition and immune activation in a Drosophila melanogaster model of human mutant tauopathy. Fecal deposit quantification and gastric emptying time courses suggested an abnormal food distribution and reduced gut motility in tau transgenic flies compared to controls. Tau transgenic flies also showed an increase in gut bacteria colony forming units (CFUs) from diluted fly homogenate, indicating an increased bacterial load. Finally, we showed that tau transgenic flies have a trend towards elevated systemic levels of antimicrobial peptides targeting gram-negative bacteria using qPCR, suggesting an enhanced innate immune response to bacterial insult. These data demonstrate qualifiable and quantifiable gut microbial and innate immune responses to tauopathy. Furthermore, these results provide a framework for future studies targeting the gut microbiome as a modifier of neurodegenerative disease.Jerrik RydbomHalea KohlVanesa R. HydeKelly M. LohrFrontiers Media S.A.articletauDrosophilagut microbiomemotilityantimicrobial peptide (AMPs)innate immune activationNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tau Drosophila gut microbiome motility antimicrobial peptide (AMPs) innate immune activation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	tau Drosophila gut microbiome motility antimicrobial peptide (AMPs) innate immune activation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Jerrik Rydbom Halea Kohl Vanesa R. Hyde Kelly M. Lohr Altered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy
description	Tau is a microtubule-associated protein that stabilizes the neuronal cytoskeleton. In the family of neurodegenerative diseases known as tauopathies, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), and chronic traumatic encephalopathy (CTE), abnormal tau aggregation destabilizes microtubule structure, contributing to a cascade of cellular processes leading to neuronal cell death. The gut microbiome has increasingly become a target of neurodegenerative disease research since gut microbiome imbalances have been linked to protein aggregation and inflammation through a bidirectional axis linking the gut and brain. Accordingly, the present study examined tau-mediated changes to gut microbiome composition and immune activation in a Drosophila melanogaster model of human mutant tauopathy. Fecal deposit quantification and gastric emptying time courses suggested an abnormal food distribution and reduced gut motility in tau transgenic flies compared to controls. Tau transgenic flies also showed an increase in gut bacteria colony forming units (CFUs) from diluted fly homogenate, indicating an increased bacterial load. Finally, we showed that tau transgenic flies have a trend towards elevated systemic levels of antimicrobial peptides targeting gram-negative bacteria using qPCR, suggesting an enhanced innate immune response to bacterial insult. These data demonstrate qualifiable and quantifiable gut microbial and innate immune responses to tauopathy. Furthermore, these results provide a framework for future studies targeting the gut microbiome as a modifier of neurodegenerative disease.
format	article
author	Jerrik Rydbom Halea Kohl Vanesa R. Hyde Kelly M. Lohr
author_facet	Jerrik Rydbom Halea Kohl Vanesa R. Hyde Kelly M. Lohr
author_sort	Jerrik Rydbom
title	Altered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy
title_short	Altered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy
title_full	Altered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy
title_fullStr	Altered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy
title_full_unstemmed	Altered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy
title_sort	altered gut microbial load and immune activation in a drosophila model of human tauopathy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2bd58d18ae3a4258b87a2935558ce5b4
work_keys_str_mv	AT jerrikrydbom alteredgutmicrobialloadandimmuneactivationinadrosophilamodelofhumantauopathy AT haleakohl alteredgutmicrobialloadandimmuneactivationinadrosophilamodelofhumantauopathy AT vanesarhyde alteredgutmicrobialloadandimmuneactivationinadrosophilamodelofhumantauopathy AT kellymlohr alteredgutmicrobialloadandimmuneactivationinadrosophilamodelofhumantauopathy
_version_	1718445503981551616

Altered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy

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