PXD020988

PXD020988 is an original dataset announced via ProteomeXchange.

Title	Gut microbiome dysregulation is associated with elevated toxic bile acids in Parkinson’s disease
Description	The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD) patients. The vermiform appendix is a lymphoid tissue implicated in the storage and regulation of the gut microbiome. Here, we investigate changes in the functional microbiome in the appendix of PD patients relative to controls by metatranscriptomic analysis. In the PD appendix, we find microbial dysbiosis affecting lipid metabolism, particularly an upregulation of bacteria responsible for secondary bile acid synthesis. Likewise, proteomic and transcript analysis in the PD gut corroborates a disruption in cholesterol homeostasis and lipid catabolism. Bile acid analysis in the PD appendix reveals an increase in the microbially-derived, toxic secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA). Synucleinopathy in mice induces similar microbiome alterations to those of PD patients and heightens microbial changes to gut inflammation. As observed in PD, the mouse model of synucleinopathy has elevated DCA and LCA. Raised levels of DCA and LCA can lead to liver injury, and an analysis of blood markers of liver dysfunction shows evidence of biliary abnormalities in PD patients, including elevated alkaline phosphatase and bilirubin. Increased bilirubin levels are also evident before PD diagnosis, in individuals at-risk of developing PD. In sum, microbially-derived toxic bile acids are heightened in PD and biliary changes may even precede the onset of overt motor symptoms.
HostingRepository	PRIDE
AnnounceDate	2021-03-04
AnnouncementXML	Submission_2021-03-04_13:05:55.629.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD020988
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	PEIPEI LI
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-18 22:58:13	ID requested
⏵ 1	2021-03-04 13:05:56	announced

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, 11(1):(2021) [pubmed]

submitter keyword: Parkinson’s disease, microbiome, bile acids, appendix, gut

Viviane Labrie
contact affiliation	Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, 49503 USA
contact email	viviane.labrie@vai.org
lab head
PEIPEI LI
contact affiliation	Van Andel Research Institute
contact email	lipeipei0611@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020988
     1. Label: PRIDE project
     2. Name: Gut microbiome dysregulation is associated with elevated toxic bile acids in Parkinson’s disease