Bile acid dehydroxylation by the gut microbiome
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ABSTRACT:
INSTRUMENT(S): Agilent 6530 QTOF
ORGANISM(S): Clostridium (ncbitaxon:1485)
SUBMITTER: 
Michael A. Fischbach
PROVIDER: MSV000085048 | MassIVE | Mon Mar 02 18:12:00 GMT 2020
REPOSITORIES: MassIVE
Publications
A metabolic pathway for bile acid dehydroxylation by the gut microbiome.
Funabashi Masanori M Grove Tyler L TL Wang Min M Varma Yug Y McFadden Molly E ME Brown Laura C LC Guo Chunjun C Higginbottom Steven S Almo Steven C SC Fischbach Michael A MA
Nature 20200617 7813
The gut microbiota synthesize hundreds of molecules, many of which influence host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at concentrations of around 500 μM and are known to block the growth of Clostridium difficile<sup>1</sup>, promote hepatocellular carcinoma<sup>2</sup> and modulate host metabolism via the G-protein-coupled receptor TGR5 (ref. <sup>3</sup>). More broadly, DCA, LCA and thei ...[more]
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Project description:A metabolic pathway for bile acid dehydroxylation by the gut microbiome
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2021-08-01 | GSE156647 | GEO
Project 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.
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