Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease

ABSTRACT Parkinson’s disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson’s disease, although a cause-effect relati...

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Autores principales:	Sarah Vascellari, Vanessa Palmas, Marta Melis, Silvia Pisanu, Roberto Cusano, Paolo Uva, Daniela Perra, Veronica Madau, Marianna Sarchioto, Valentina Oppo, Nicola Simola, Micaela Morelli, Maria Laura Santoru, Luigi Atzori, Maurizio Melis, Giovanni Cossu, Aldo Manzin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	16S RNA gut microbiota PD metabolome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/809869bcae4e4aafac202dd23e421b0b
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spelling	oai:doaj.org-article:809869bcae4e4aafac202dd23e421b0b2021-12-02T18:15:47ZGut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease10.1128/mSystems.00561-202379-5077https://doaj.org/article/809869bcae4e4aafac202dd23e421b0b2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00561-20https://doaj.org/toc/2379-5077ABSTRACT Parkinson’s disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson’s disease, although a cause-effect relationship remains to be established. Herein, the gut microbiota composition of 64 Italian patients with Parkinson’s disease and 51 controls was determined using a next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry was also investigated. The most significant changes within the Parkinson’s disease group highlighted a reduction in bacterial taxa, which are linked to anti-inflammatory/neuroprotective effects, particularly in the Lachnospiraceae family and key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, and Blautia. The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. Changes were seen in lipids (linoleic acid, oleic acid, succinic acid, and sebacic acid), vitamins (pantothenic acid and nicotinic acid), amino acids (isoleucine, leucine, phenylalanine, glutamic acid, and pyroglutamic acid) and other organic compounds (cadaverine, ethanolamine, and hydroxy propionic acid). Most modified metabolites strongly correlated with the abundance of members belonging to the Lachnospiraceae family, suggesting that these gut bacteria correlate with altered metabolism rates in Parkinson’s disease. IMPORTANCE To our knowledge, this is one of the few studies thus far that correlates the composition of the gut microbiota with the direct analysis of fecal metabolites in patients with Parkinson’s disease. Overall, our data highlight microbiota modifications correlated with numerous fecal metabolites. This suggests that Parkinson’s disease is associated with gut dysregulation that involves a synergistic relationship between gut microbes and several bacterial metabolites favoring altered homeostasis. Interestingly, a reduction of short-chain fatty acid (SCFA)-producing bacteria influenced the shape of the metabolomics profile, affecting several metabolites with potential protective effects in the Parkinson group. On the other hand, the extensive impact that intestinal dysbiosis has at the level of numerous metabolic pathways could encourage the identification of specific biomarkers for the diagnosis and treatment of Parkinson’s disease, also in light of the effect that specific drugs have on the composition of the intestinal microbiota.Sarah VascellariVanessa PalmasMarta MelisSilvia PisanuRoberto CusanoPaolo UvaDaniela PerraVeronica MadauMarianna SarchiotoValentina OppoNicola SimolaMicaela MorelliMaria Laura SantoruLuigi AtzoriMaurizio MelisGiovanni CossuAldo ManzinAmerican Society for Microbiologyarticle16S RNAgut microbiotaPDmetabolomeMicrobiologyQR1-502ENmSystems, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	16S RNA gut microbiota PD metabolome Microbiology QR1-502
spellingShingle	16S RNA gut microbiota PD metabolome Microbiology QR1-502 Sarah Vascellari Vanessa Palmas Marta Melis Silvia Pisanu Roberto Cusano Paolo Uva Daniela Perra Veronica Madau Marianna Sarchioto Valentina Oppo Nicola Simola Micaela Morelli Maria Laura Santoru Luigi Atzori Maurizio Melis Giovanni Cossu Aldo Manzin Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease
description	ABSTRACT Parkinson’s disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson’s disease, although a cause-effect relationship remains to be established. Herein, the gut microbiota composition of 64 Italian patients with Parkinson’s disease and 51 controls was determined using a next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry was also investigated. The most significant changes within the Parkinson’s disease group highlighted a reduction in bacterial taxa, which are linked to anti-inflammatory/neuroprotective effects, particularly in the Lachnospiraceae family and key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, and Blautia. The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. Changes were seen in lipids (linoleic acid, oleic acid, succinic acid, and sebacic acid), vitamins (pantothenic acid and nicotinic acid), amino acids (isoleucine, leucine, phenylalanine, glutamic acid, and pyroglutamic acid) and other organic compounds (cadaverine, ethanolamine, and hydroxy propionic acid). Most modified metabolites strongly correlated with the abundance of members belonging to the Lachnospiraceae family, suggesting that these gut bacteria correlate with altered metabolism rates in Parkinson’s disease. IMPORTANCE To our knowledge, this is one of the few studies thus far that correlates the composition of the gut microbiota with the direct analysis of fecal metabolites in patients with Parkinson’s disease. Overall, our data highlight microbiota modifications correlated with numerous fecal metabolites. This suggests that Parkinson’s disease is associated with gut dysregulation that involves a synergistic relationship between gut microbes and several bacterial metabolites favoring altered homeostasis. Interestingly, a reduction of short-chain fatty acid (SCFA)-producing bacteria influenced the shape of the metabolomics profile, affecting several metabolites with potential protective effects in the Parkinson group. On the other hand, the extensive impact that intestinal dysbiosis has at the level of numerous metabolic pathways could encourage the identification of specific biomarkers for the diagnosis and treatment of Parkinson’s disease, also in light of the effect that specific drugs have on the composition of the intestinal microbiota.
format	article
author	Sarah Vascellari Vanessa Palmas Marta Melis Silvia Pisanu Roberto Cusano Paolo Uva Daniela Perra Veronica Madau Marianna Sarchioto Valentina Oppo Nicola Simola Micaela Morelli Maria Laura Santoru Luigi Atzori Maurizio Melis Giovanni Cossu Aldo Manzin
author_facet	Sarah Vascellari Vanessa Palmas Marta Melis Silvia Pisanu Roberto Cusano Paolo Uva Daniela Perra Veronica Madau Marianna Sarchioto Valentina Oppo Nicola Simola Micaela Morelli Maria Laura Santoru Luigi Atzori Maurizio Melis Giovanni Cossu Aldo Manzin
author_sort	Sarah Vascellari
title	Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease
title_short	Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease
title_full	Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease
title_fullStr	Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease
title_full_unstemmed	Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease
title_sort	gut microbiota and metabolome alterations associated with parkinson’s disease
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/809869bcae4e4aafac202dd23e421b0b
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Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease

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