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Open AccessArticle

Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease

1
Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA
2
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA
3
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA
4
Metabolomics Department, Beaumont Health, Royal Oak, MI 48073, USA
5
Department of Obstetrics and Gynecology, Oakland University-William Beaumont School Medicine, Rochester, MI 48309, USA
6
Integrated Mass Spectrometry Unit, Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA
7
Department of Pathology, Oregon Health & Science University, Portland, OR 97239, USA
8
Division of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA
*
Author to whom correspondence should be addressed.
Metabolites 2021, 11(1), 29; https://doi.org/10.3390/metabo11010029
Received: 26 November 2020 / Revised: 25 December 2020 / Accepted: 28 December 2020 / Published: 4 January 2021
(This article belongs to the Special Issue Metabolomics in Human Tissues and Materials II)
The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD). The vermiform appendix is a lymphoid tissue in the cecum implicated in the storage and regulation of the gut microbiota. We sought to determine whether the appendix microbiome is altered in PD and to analyze the biological consequences of the microbial alterations. We investigated the changes in the functional microbiota in the appendix of PD patients relative to controls (n = 12 PD, 16 C) by metatranscriptomic analysis. We found microbial dysbiosis affecting lipid metabolism, including an upregulation of bacteria responsible for secondary bile acid synthesis. We then quantitatively measure changes in bile acid abundance in PD relative to the controls in the appendix (n = 15 PD, 12 C) and ileum (n = 20 PD, 20 C). Bile acid analysis in the PD appendix reveals an increase in hydrophobic and secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA). Further proteomic and transcriptomic analysis in the appendix and ileum corroborated these findings, highlighting changes in the PD gut that are consistent with a disruption in bile acid control, including alterations in mediators of cholesterol homeostasis and lipid metabolism. Microbially derived toxic bile acids are heightened in PD, which suggests biliary abnormalities may play a role in PD pathogenesis. View Full-Text
Keywords: Parkinson’s disease; microbiome; bile acids; appendix; gut Parkinson’s disease; microbiome; bile acids; appendix; gut
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MDPI and ACS Style

Li, P.; Killinger, B.A.; Ensink, E.; Beddows, I.; Yilmaz, A.; Lubben, N.; Lamp, J.; Schilthuis, M.; Vega, I.E.; Woltjer, R.; Pospisilik, J.A.; Brundin, P.; Brundin, L.; Graham, S.F.; Labrie, V. Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease. Metabolites 2021, 11, 29.

AMA Style

Li P, Killinger BA, Ensink E, Beddows I, Yilmaz A, Lubben N, Lamp J, Schilthuis M, Vega IE, Woltjer R, Pospisilik JA, Brundin P, Brundin L, Graham SF, Labrie V. Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease. Metabolites. 2021; 11(1):29.

Chicago/Turabian Style

Li, Peipei; Killinger, Bryan A.; Ensink, Elizabeth; Beddows, Ian; Yilmaz, Ali; Lubben, Noah; Lamp, Jared; Schilthuis, Meghan; Vega, Irving E.; Woltjer, Randy; Pospisilik, J. A.; Brundin, Patrik; Brundin, Lena; Graham, Stewart F.; Labrie, Viviane. 2021. "Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease" Metabolites 11, no. 1: 29.

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