Exploring human-genome gut-microbiome interaction in Parkinson’s disease

Abstract The causes of complex diseases remain an enigma despite decades of epidemiologic research on environmental risks and genome-wide studies that have uncovered tens or hundreds of susceptibility loci for each disease. We hypothesize that the microbiome is the missing link. Genetic studies have...

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Autores principales:	Zachary D. Wallen, William J. Stone, Stewart A. Factor, Eric Molho, Cyrus P. Zabetian, David G. Standaert, Haydeh Payami
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/3c0a6ff80f1c4756b10bac34c75cba2d
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spelling	oai:doaj.org-article:3c0a6ff80f1c4756b10bac34c75cba2d2021-12-02T18:51:47ZExploring human-genome gut-microbiome interaction in Parkinson’s disease10.1038/s41531-021-00218-22373-8057https://doaj.org/article/3c0a6ff80f1c4756b10bac34c75cba2d2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00218-2https://doaj.org/toc/2373-8057Abstract The causes of complex diseases remain an enigma despite decades of epidemiologic research on environmental risks and genome-wide studies that have uncovered tens or hundreds of susceptibility loci for each disease. We hypothesize that the microbiome is the missing link. Genetic studies have shown that overexpression of alpha-synuclein, a key pathological protein in Parkinson’s disease (PD), can cause familial PD and variants at alpha-synuclein locus confer risk of idiopathic PD. Recently, dysbiosis of gut microbiome in PD was identified: altered abundances of three microbial clusters were found, one of which was composed of opportunistic pathogens. Using two large datasets, we found evidence that the overabundance of opportunistic pathogens in PD gut is influenced by the host genotype at the alpha-synuclein locus, and that the variants responsible modulate alpha-synuclein expression. Results put forth testable hypotheses on the role of gut microbiome in the pathogenesis of PD, the incomplete penetrance of PD susceptibility genes, and potential triggers of pathology in the gut.Zachary D. WallenWilliam J. StoneStewart A. FactorEric MolhoCyrus P. ZabetianDavid G. StandaertHaydeh PayamiNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 Zachary D. Wallen William J. Stone Stewart A. Factor Eric Molho Cyrus P. Zabetian David G. Standaert Haydeh Payami Exploring human-genome gut-microbiome interaction in Parkinson’s disease
description	Abstract The causes of complex diseases remain an enigma despite decades of epidemiologic research on environmental risks and genome-wide studies that have uncovered tens or hundreds of susceptibility loci for each disease. We hypothesize that the microbiome is the missing link. Genetic studies have shown that overexpression of alpha-synuclein, a key pathological protein in Parkinson’s disease (PD), can cause familial PD and variants at alpha-synuclein locus confer risk of idiopathic PD. Recently, dysbiosis of gut microbiome in PD was identified: altered abundances of three microbial clusters were found, one of which was composed of opportunistic pathogens. Using two large datasets, we found evidence that the overabundance of opportunistic pathogens in PD gut is influenced by the host genotype at the alpha-synuclein locus, and that the variants responsible modulate alpha-synuclein expression. Results put forth testable hypotheses on the role of gut microbiome in the pathogenesis of PD, the incomplete penetrance of PD susceptibility genes, and potential triggers of pathology in the gut.
format	article
author	Zachary D. Wallen William J. Stone Stewart A. Factor Eric Molho Cyrus P. Zabetian David G. Standaert Haydeh Payami
author_facet	Zachary D. Wallen William J. Stone Stewart A. Factor Eric Molho Cyrus P. Zabetian David G. Standaert Haydeh Payami
author_sort	Zachary D. Wallen
title	Exploring human-genome gut-microbiome interaction in Parkinson’s disease
title_short	Exploring human-genome gut-microbiome interaction in Parkinson’s disease
title_full	Exploring human-genome gut-microbiome interaction in Parkinson’s disease
title_fullStr	Exploring human-genome gut-microbiome interaction in Parkinson’s disease
title_full_unstemmed	Exploring human-genome gut-microbiome interaction in Parkinson’s disease
title_sort	exploring human-genome gut-microbiome interaction in parkinson’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3c0a6ff80f1c4756b10bac34c75cba2d
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Exploring human-genome gut-microbiome interaction in Parkinson’s disease

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