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Gut microbiome dysbiosis is associated with elevated toxic bile acids in Parkinson’s disease
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Gut microbiome dysbiosis is associated with elevated toxic bile acids in Parkinson’s disease
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Paper
Gut microbiome dysbiosis is associated with elevated toxic bile acids in Parkinson’s disease
2020
Overview
Abstract The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD) patients. Here, we investigate changes in the functional microbiome in the appendix of PD patients relative to controls by metatranscriptomic analysis. We find microbial dysbiosis affecting lipid metabolism, particularly an upregulation of bacteria responsible for secondary bile acid synthesis. Proteomic and transcript analysis corroborates a disruption in cholesterol homeostasis and lipid catabolism. Bile acid analysis reveals an increase in microbially-derived, toxic secondary bile acids. Synucleinopathy in mice induces similar microbiome alterations to those of PD patients. The mouse model of synucleinopathy has elevated DCA and LCA. An analysis of blood markers shows evidence of biliary abnormalities early in PD, including elevated alkaline phosphatase and bilirubin. Increased bilirubin levels are also evident before PD diagnosis. In sum, microbially-derived toxic bile acids are heightened in PD and biliary changes may even precede the onset of overt motor symptoms. Competing Interest Statement MB is a full-time employee at Roche and may additionally hold Roche stock/stock options. P.B. has received commercial support as a consultant from Axial Biotherapeutics, Calico, CuraSen, Fujifilm-Cellular Dynamics International, IOS Press Partners, LifeSci Capital LLC, Lundbeck A/S, Idorsia and Living Cell Technologies LTD. He has received commercial support for grants/research from Lundbeck A/S and Roche. He has ownership interests in Acousort AB and Axial Biotherapeutics and is on the steering committee of the NILO-PD trial. No other authors have conflicts of interest.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
Subject
