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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number29
Pages (from-to)1-15
Number of pages15
JournalMetabolites
Volume11
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • Appendix
  • Bile acids
  • Gut
  • Microbiome
  • Parkinson’s disease

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology

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