Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease
Peipei Li,
Bryan A. Killinger,
Elizabeth Ensink,
Ian Beddows,
Ali Yilmaz,
Noah Lubben,
Jared Lamp,
Meghan Schilthuis,
Irving E. Vega,
Randy Woltjer,
J. Andrew Pospisilik,
Patrik Brundin,
Lena Brundin,
Stewart F. Graham,
Viviane Labrie
Affiliations
Peipei Li
Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA
Bryan A. Killinger
Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA
Elizabeth Ensink
Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA
Ian Beddows
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA
Ali Yilmaz
Metabolomics Department, Beaumont Health, Royal Oak, MI 48073, USA
Noah Lubben
Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA
Jared Lamp
Integrated Mass Spectrometry Unit, Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA
Meghan Schilthuis
Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA
Irving E. Vega
Integrated Mass Spectrometry Unit, Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA
Randy Woltjer
Department of Pathology, Oregon Health & Science University, Portland, OR 97239, USA
J. Andrew Pospisilik
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA
Patrik Brundin
Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA
Lena Brundin
Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA
Stewart F. Graham
Metabolomics Department, Beaumont Health, Royal Oak, MI 48073, USA
Viviane Labrie
Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA
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.
