Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease
| Autor: | Stewart F. Graham, Meghan Schilthuis, Noah Lubben, Randy Woltjer, Viviane Labrie, Patrik Brundin, Peipei Li, Jared Lamp, Elizabeth Ensink, Lena Brundin, Bryan A. Killinger, Irving E. Vega, Ali Yilmaz, J. Andrew Pospisilik, Ian Beddows |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Lithocholic acid medicine.drug_class Endocrinology Diabetes and Metabolism lcsh:QR1-502 microbiome Gut flora appendix Biochemistry digestive system lcsh:Microbiology Article 03 medical and health sciences chemistry.chemical_compound Cecum 0302 clinical medicine Internal medicine medicine Microbiome Molecular Biology bile acids Parkinson’s disease gut Bile acid biology Deoxycholic acid digestive oral and skin physiology fungi food and beverages Lipid metabolism biology.organism_classification medicine.disease nervous system diseases 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Dysbiosis 030217 neurology & neurosurgery |
| Zdroj: | Metabolites; Volume 11; Issue 1; Pages: 29 Metabolites Metabolites, Vol 11, Iss 29, p 29 (2021) |
| ISSN: | 2218-1989 |
| DOI: | 10.3390/metabo11010029 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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