Summary of Study ST000998

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000675. The data can be accessed directly via it's Project DOI: 10.21228/M8DX19 This work is supported by NIH grant, U2C- DK119886.

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Study IDST000998
Study TitleBile Acid of Primary Sclerosing Cholangitis (part IV)
Study SummaryTo qualitatively and quantitatively analyze enterohepatically-circulated molecules using targeted bile acid concentrations of peripheral blood collected from primary sclerosing cholangitis (PSC) patients compared to normal and diseased controls. There are three groups of patients. (1) Normal donor controls (ND), (2) Patients with Primary Sclerosing Cholangitis (PSC), and (3) Disease Controls (DC) which are patients with liver disease other than PSC.
Institute
Mayo Clinic
Last NameO'Hara
First NameSteven
Address200 First St. SW, Rochester, Minnesota, 55905, USA
Emailohara.steven@mayo.edu
Phone507-284-1006
Submit Date2017-07-05
Raw Data AvailableYes
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2019-07-17
Release Version1
Steven O'Hara Steven O'Hara
https://dx.doi.org/10.21228/M8DX19
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000675
Project DOI:doi: 10.21228/M8DX19
Project Title:Mayo Pilot and Feasibility: The Enterohepatic Metabolome in Primary Sclerosing Cholangitis
Project Summary:Emerging in vitro and in vivo data, including work from our laboratory and clinical research group, suggest fundamental pathophysiologic mechanisms in primary sclerosing cholangitis (PSC) that are centered on the enterohepatic circulation of gut-derived molecules. Therefore, in this proposal, we will test the central hypothesis that increased pathologic enterohepatic circulation of enteric metabolites which trigger specific pro-fibroinflammatory hepatobiliary responses are centrally involved in the etiopathogenesis of primary sclerosing cholangitis (PSC). While these processes have been hypothesized to play a significant role in the initiation, progression, and adverse clinical sequelae of PSC, they have not been directly tested to date. In our proposal, we will experimentally address the nature and extent of the metabolomic profiles of portal and peripheral blood as well as bile in patients with PSC. We will perform qualitative and quantitative ultra-performance liquid chromatography/mass spectroscopy-based metabolomic analyses to determine metabolic changes in portal and peripheral plasma and bile. Through subsequent pathway analyses we intend to identify metabolic enzymes and known biochemical pathways that may be altered in PSC. We anticipate that patients with PSC will have distinct alterations in the portal venous and bile metabolomic profiles and associated signaling pathways compared to normal and disease controls; and these alterations may be amenable to pharmacologic manipulation and future therapies.
Institute:Mayo Clinic
Last Name:O'Hara
First Name:Steven
Address:200 First St. SW, Rochester, Minnesota, 55905, USA
Email:ohara.steven@mayo.edu
Phone:507-284-1006

Subject:

Subject ID:SU001037
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Grouping
SA061744ms6724-23DC
SA061745ms6724-24DC
SA061746ms6724-25DC
SA061747ms6724-22DC
SA061748ms6724-21DC
SA061749ms6724-19DC
SA061750ms6724-20DC
SA061751ms6724-26DC
SA061752ms6724-27DC
SA061753ms6724-32DC
SA061754ms6724-33DC
SA061755ms6724-31DC
SA061756ms6724-30DC
SA061757ms6724-28DC
SA061758ms6724-29DC
SA061759ms6724-18DC
SA061760ms6724-17DC
SA061761ms6724-16DC
SA061762ms6724-1ND
SA061763ms6724-9ND
SA061764ms6724-8ND
SA061765ms6724-6ND
SA061766ms6724-4ND
SA061767ms6724-2ND
SA061768ms6724-3ND
SA061769ms6724-7ND
SA061770ms6724-5ND
SA061771ms6724-10PSC
SA061772ms6724-15PSC
SA061773ms6724-14PSC
SA061774ms6724-13PSC
SA061775ms6724-12PSC
SA061776ms6724-11PSC
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Collection:

Collection ID:CO001031
Collection Summary:After obtaining informed consent, portal and peripheral venous blood (4 ml of each) and bile (2 mL) was collected intraoperatively in a red-top tube by a Mayo Clinic LT surgeon. Blood was placed on ice, promptly fractionated by centrifugation, divided into 100 μL aliquots, and stored at -80°C.
Sample Type:Blood (serum)

Treatment:

Treatment ID:TR001051
Treatment Summary: We prospectively enrolled three groups of participants from the Mayo Clinic Liver Transplant inpatient service and outpatient clinics and have collected samples from: i) 9 patients with PSC who underwent living- donor LT, ii) 15 donors (normal controls), and iii) 20 patients with cirrhosis due to a disorder other than PSC who underwent LT (disease controls). The following inclusion and exclusion criteria were applied: Inclusion criteria 1. Adult (age>18 years). 2. PSC patient undergoing LT, healthy living donor, or other chronic liver disease patient undergoing LT. Exclusion Criteria: 1. Females who are pregnant or attempting to become pregnant. 2. Concomitant liver disease (e.g. chronic viral hepatitis in addition to PSC). 3. Acute intestinal disease (infectious enterocolitis, IBD flare) in the past 6 months. 4. Treatment with any investigational drugs within the past 6 months. 5. Use of antibiotics within the past 4 weeks. 6. Any previous organ transplant. 7. Hemodialysis.

Sample Preparation:

Sampleprep ID:SP001044
Sampleprep Summary:bile acid concentrations

Combined analysis:

Analysis ID AN001627
Analysis type MS
Chromatography type HILIC
Chromatography system Cohesive TX2
Column Altma HP HILIC (150 x 2.1mm,5um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name ABI Sciex 6500 QTrap
Ion Mode POSITIVE
Units uM

Chromatography:

Chromatography ID:CH001145
Instrument Name:Cohesive TX2
Column Name:Altma HP HILIC (150 x 2.1mm,5um)
Chromatography Type:HILIC

MS:

MS ID:MS001503
Analysis ID:AN001627
Instrument Name:ABI Sciex 6500 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:uM
Ion Mode:POSITIVE
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