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Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease
Metabolites (2021)
  • Peipei Li, Van Andel Institute
  • Bryan A. Killinger, Rush University Medical Center
  • Bryan A. Killinger, Van Andel Institute
  • Elizabeth Ensink, Van Andel Institute
  • Ian Beddows, Van Andel Institute
  • Ali Yilmaz, Oakland University
  • Ali Yilmaz, Beaumont Health
  • Noah Lubben, Van Andel Institute
  • Jared Lamp, Michigan State University
  • Meghan Schilthuis, Van Andel Institute
  • Irving E. Vega, Michigan State University
  • Randy Woltjer, Oregon Health & Science University
  • J. Andrew Pospisilik, Van Andel Institute
  • Patrik Brundin, Michigan State University
  • Patrik Brundin, Van Andel Institute
  • Lena Brundin, Michigan State University
  • Lena Brundin, Van Andel Institute
  • Stewart F. Graham, Oakland University
  • Stewart F. Graham, Beaumont Health
  • Viviane Labrie, Michigan State University
  • Viviane Labrie, Van Andel Institute
Abstract
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.
Keywords
  • Parkinson’s disease,
  • appendix,
  • bile acids,
  • gut,
  • microbiome
Publication Date
January 4, 2021
DOI
10.3390/METABO11010029
Citation Information
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 Jan 4;11(1):29. doi: 10.3390/metabo11010029. PMID: 33406628; PMCID: PMC7823437.