Production of the Neurotoxin Salsolinol by a Gut-Associated Bacterium and Its Modulation by Alcohol

Utilizing a simulated gastrointestinal medium which approximates physiological conditions within the mammalian GI tract, experiments aimed at isolating and identifying unique microbial metabolites were conducted. These efforts led to the finding that Escherichia coli, a common member of the gut micr...

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Main Authors: Daniel N. Villageliú, David J. Borts, Mark Lyte
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-12-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2018.03092/full
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author Daniel N. Villageliú
Daniel N. Villageliú
David J. Borts
Mark Lyte
author_facet Daniel N. Villageliú
Daniel N. Villageliú
David J. Borts
Mark Lyte
author_sort Daniel N. Villageliú
collection DOAJ
description Utilizing a simulated gastrointestinal medium which approximates physiological conditions within the mammalian GI tract, experiments aimed at isolating and identifying unique microbial metabolites were conducted. These efforts led to the finding that Escherichia coli, a common member of the gut microbiota, is capable of producing significant quantities of salsolinol. Salsolinol is a neuroactive compound which has been investigated as a potential contributor to the development of neurodegenerative diseases such as Parkinson’s disease (PD). However the origin of salsolinol within the body has remained highly contested. We herein report the first demonstration that salsolinol can be made in vitro in response to microbial activity. We detail the isolation and identification of salsolinol produced by E. coli, which is capable of producing salsolinol in the presence of dopamine with production enhanced in the presence of alcohol. That this discovery was found in a medium that approximates gut conditions suggests that microbial salsolinol production could exist in the gut. This discovery lays the ground work for follow up in vivo investigations to explore whether salsolinol production is a mechanism by which the microbiota may influence the host. As salsolinol has been implicated in the pathogenesis of PD, this work may be relevant, for example, to investigators who have suggested that the development of PD may have a gut origin. This report suggests, but does not establish, an alternative microbiota-based mechanism to explain how the gut may play a critical role in the development of PD as well other conditions involving altered neuronal function due to salsolinol-induced neurotoxicity.
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spelling doaj.art-b05eacd510e04b2d9f2cc1cb543776b72022-12-21T19:03:36ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-12-01910.3389/fmicb.2018.03092426521Production of the Neurotoxin Salsolinol by a Gut-Associated Bacterium and Its Modulation by AlcoholDaniel N. Villageliú0Daniel N. Villageliú1David J. Borts2Mark Lyte3Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesInterdepartmental Microbiology Graduate Program, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesDepartment of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesDepartment of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesUtilizing a simulated gastrointestinal medium which approximates physiological conditions within the mammalian GI tract, experiments aimed at isolating and identifying unique microbial metabolites were conducted. These efforts led to the finding that Escherichia coli, a common member of the gut microbiota, is capable of producing significant quantities of salsolinol. Salsolinol is a neuroactive compound which has been investigated as a potential contributor to the development of neurodegenerative diseases such as Parkinson’s disease (PD). However the origin of salsolinol within the body has remained highly contested. We herein report the first demonstration that salsolinol can be made in vitro in response to microbial activity. We detail the isolation and identification of salsolinol produced by E. coli, which is capable of producing salsolinol in the presence of dopamine with production enhanced in the presence of alcohol. That this discovery was found in a medium that approximates gut conditions suggests that microbial salsolinol production could exist in the gut. This discovery lays the ground work for follow up in vivo investigations to explore whether salsolinol production is a mechanism by which the microbiota may influence the host. As salsolinol has been implicated in the pathogenesis of PD, this work may be relevant, for example, to investigators who have suggested that the development of PD may have a gut origin. This report suggests, but does not establish, an alternative microbiota-based mechanism to explain how the gut may play a critical role in the development of PD as well other conditions involving altered neuronal function due to salsolinol-induced neurotoxicity.https://www.frontiersin.org/article/10.3389/fmicb.2018.03092/fullsalsolinolParkinson’s diseasemicrobial metabolic activitygut-brain-axis communicationgut origin for Parkinson’s disease
spellingShingle Daniel N. Villageliú
Daniel N. Villageliú
David J. Borts
Mark Lyte
Production of the Neurotoxin Salsolinol by a Gut-Associated Bacterium and Its Modulation by Alcohol
Frontiers in Microbiology
salsolinol
Parkinson’s disease
microbial metabolic activity
gut-brain-axis communication
gut origin for Parkinson’s disease
title Production of the Neurotoxin Salsolinol by a Gut-Associated Bacterium and Its Modulation by Alcohol
title_full Production of the Neurotoxin Salsolinol by a Gut-Associated Bacterium and Its Modulation by Alcohol
title_fullStr Production of the Neurotoxin Salsolinol by a Gut-Associated Bacterium and Its Modulation by Alcohol
title_full_unstemmed Production of the Neurotoxin Salsolinol by a Gut-Associated Bacterium and Its Modulation by Alcohol
title_short Production of the Neurotoxin Salsolinol by a Gut-Associated Bacterium and Its Modulation by Alcohol
title_sort production of the neurotoxin salsolinol by a gut associated bacterium and its modulation by alcohol
topic salsolinol
Parkinson’s disease
microbial metabolic activity
gut-brain-axis communication
gut origin for Parkinson’s disease
url https://www.frontiersin.org/article/10.3389/fmicb.2018.03092/full
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