Summary of Study ST002471

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 PR001596. The data can be accessed directly via it's Project DOI: 10.21228/M8D701 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002471
Study TitleLinking bacterial metabolites to disease-associated microbes to uncover mechanisms of host-microbial interactions in intestinal inflammation. Human stool profiling
Study SummaryUnderstanding the role of the gut microbiome in inflammatory and autoimmune diseases requires the identification of microbial molecular effectors and their link to host pathophysiology. Here, we present a framework to identify and characterize novel microbial metabolites in patient samples and to directly link their production to disease-associated microbes. We applied this approach to investigate the spectrum of disease severity and treatment response in ulcerative colitis (UC) using longitudinal metabolite and strain profiles combined with paired plasma profiles.
Institute
Broad Institute of MIT and Harvard
Last NameXavier
First NameRamnik
Address415 Main Street
Emailrxavier@broadinstitute.org
Phone617717084
Submit Date2023-02-09
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-02-12
Release Version1
Ramnik Xavier Ramnik Xavier
https://dx.doi.org/10.21228/M8D701
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001596
Project DOI:doi: 10.21228/M8D701
Project Title:Linking bacterial metabolites to disease-associated microbes to uncover mechanisms of host-microbial interactions in intestinal inflammation
Project Type:Metabolomic profiling of human fecal and plasma samples and bacterial strains
Project Summary:Understanding the role of the gut microbiome in inflammatory and autoimmune diseases requires the identification of microbial molecular effectors and their link to host pathophysiology. Here, we present a framework to identify and characterize novel microbial metabolites in patient samples and to directly link their production to disease-associated microbes. We applied this approach to investigate the spectrum of disease severity and treatment response in ulcerative colitis (UC) using longitudinal metabolite and strain profiles combined with paired plasma profiles.
Institute:Broad Institute of MIT and Harvard
Last Name:Xavier
First Name:Ramnik
Address:415 Main Street
Email:rxavier@broadinstitute.org
Phone:6177147080
Publications:Schirmer, M., Stražar, M., Avila-Pacheco, J., Rojas-Tapias, D. F., Brown, E. M., Temple, E., Deik, A., Bullock, K., Jeanfavre, S., Pierce, K., Jin, S., Invernizzi, R., Pust, M.-M., Costliow, Z., Mack, D. R., Griffiths, A. M., Walters, T., Boyle, B. M., Kugathasan, S., … Xavier, R. J. (2024). Linking microbial genes to plasma and stool metabolites uncovers host-microbial interactions underlying ulcerative colitis disease course. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2023.12.013
Contributors:Melanie Schirmer, Martin Strazar, Julian Avila-Pacheco, Daniel F. Rojas-Tapias, Eric Brown, Emily Temple, Subra Kugathasan, Zach Costliow, Hera Vlamakis, Jeff Hyams, Lee Denson, Clary B. Clish, Ramnik J. Xavier

Subject:

Subject ID:SU002561
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 collectionWeek PUCAI_C3_WKall
SA247608STL107620 mild
SA247609STL105750 mild
SA247610STL108110 mild
SA247611STL108960 mild
SA247612STL110890 mild
SA247613STL103230 mild
SA247614STL108770 mild
SA247615STL108600 mild
SA247616STL101770 mild
SA247617STL101910 mild
SA247618STL102790 mild
SA247619STL101800 mild
SA247620STL110400 moderate/severe
SA247621STL110210 moderate/severe
SA247622STL109150 moderate/severe
SA247623STL110410 moderate/severe
SA247624STL110570 moderate/severe
SA247625STL100370 moderate/severe
SA247626STL100220 moderate/severe
SA247627STL111220 moderate/severe
SA247628STL101260 moderate/severe
SA247629STL110800 moderate/severe
SA247630STL110730 moderate/severe
SA247631STL109560 moderate/severe
SA247632STL105620 moderate/severe
SA247633STL102630 moderate/severe
SA247634STL108840 moderate/severe
SA247635STL104580 moderate/severe
SA247636STL104050 moderate/severe
SA247637STL105900 moderate/severe
SA247638STL105040 moderate/severe
SA247639STL106030 moderate/severe
SA247640STL107930 moderate/severe
SA247641STL108360 moderate/severe
SA247642STL107050 moderate/severe
SA247643STL102400 moderate/severe
SA247644STL2049712 inactive
SA247645STL2048112 inactive
SA247646STL2046112 inactive
SA247647STL2052212 inactive
SA247648STL2065312 inactive
SA247649STL2067212 inactive
SA247650STL2064412 inactive
SA247651STL2063112 inactive
SA247652STL2063012 inactive
SA247653STL2037812 inactive
SA247654STL2001412 inactive
SA247655STL2013612 inactive
SA247656STL2011712 inactive
SA247657STL2011212 inactive
SA247658STL2018512 inactive
SA247659STL2029212 inactive
SA247660STL2031612 inactive
SA247661STL2027612 inactive
SA247662STL4059312 mild
SA247663STL4055412 mild
SA247664STL2065412 mild
SA247665STL2064812 mild
SA247666STL2018412 moderate/severe
SA247667STL2053912 moderate/severe
SA247668STL404874 inactive
SA247669STL406734 inactive
SA247670STL405354 inactive
SA247671STL405714 inactive
SA247672STL402804 inactive
SA247673STL405214 inactive
SA247674STL400664 inactive
SA247675STL400014 inactive
SA247676STL400404 inactive
SA247677STL400174 inactive
SA247678STL401774 inactive
SA247679STL401804 inactive
SA247680STL407014 inactive
SA247681STL402294 inactive
SA247682STL407164 mild
SA247683STL405954 mild
SA247684STL406914 mild
SA247685STL406264 mild
SA247686STL402444 mild
SA247687STL407204 mild
SA247688STL400144 mild
SA247689STL404374 mild
SA247690STL405114 mild
SA247691STL405394 mild
SA247692STL405554 mild
SA247693STL404554 moderate/severe
SA247694STL406354 moderate/severe
SA247695STL5016052 inactive
SA247696STL5052052 inactive
SA247697STL5042552 moderate/severe
SA247698STL5031552 moderate/severe
Showing results 1 to 91 of 91

Collection:

Collection ID:CO002554
Collection Summary:Pediatric UC patients (4-17 years of age) were recruited between July 2012 and April 2015 from 29 centers in the USA and Canada and monitored over the course of one year. Patients were treatment-naive at week 0 and received either 5-aminosalicylic acid (mesalamine) or oral/intravenous corticosteroids followed by mesalamine. Up to 4 samples were collected from each patient (week 0, 4, 12 and 52). In addition, metadata and clinical data were collected, including age, gender, ethnicity, treatment, Pediatric Ulcerative Colitis Activity Index (PUCAI), disease progression (colectomy and remission status) and fecal calprotectin (ELISA). Stool samples were frozen at -20 degrees at time of collection by study participants and transported back to the site via freezer gel packs and shipping containers to keep samples frozen during transport. Once at the site, samples were frozen at -80 degrees and batched-shipped with dry ice overnight to the biorepository.
Sample Type:Feces

Treatment:

Treatment ID:TR002573
Treatment Summary:NA

Sample Preparation:

Sampleprep ID:SP002567
Sampleprep Summary:Stool samples were homogenized in 10 μL of water per milligram stool sample weight using a bead mill (TissueLyser II; Qiagen) and the aqueous homogenates were aliquoted for metabolite profiling analyses. LC-MS samples were prepared for four profiling methods as follows: HILIC-pos: Metabolites were extracted by adding 90 μL of 74.9:24.9:0.2 v/v/v acetonitrile/methanol/formic acid containing stable isotope-labeled internal standards (valine-d8, Isotec; and phenylalanine-d8, Cambridge Isotope Laboratories; Andover, MA) to a 10 μL aliquot of stool homogenate or plasma. Samples were vortexed and then centrifuged (10 min, 9,000 x g, 4°C) to pellet protein precipitates. Supernatants were transferred to glass autosampler vials containing inserts for LC-MS analysis. C8-pos: Lipids were extracted by adding 190 μL of isopropanol containing 1-dodecanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine as an internal standard (Avanti Polar Lipids; Alabaster, AL) to a 10 μL aliquot of stool homogenate or plasma. Samples were vortexed and then centrifuged (10 min, 9,000 x g, ambient temperature) to pellet protein precipitates. Supernatants were transferred to glass autosampler vials containing inserts for LC-MS analysis. HILIC-neg: Metabolites were extracted by adding 120 μL of 80% methanol containing inosine-15N4, thymine-d4 and glycocholate-d4 internal standards (Cambridge Isotope Laboratories; Andover, MA) to a 30 μL aliquot of stool homogenate or plasma. Samples were vortexed and then centrifuged (10 min, 9,000 x g, 4°C) to pellet protein precipitates. Supernatants were transferred to glass autosampler vials containing inserts for LC-MS analysis. C18-neg: Metabolites were extracted by adding 90 μL of methanol containing PGE2-d4 as an internal standard (Cayman Chemical Co.; Ann Arbor, MI) to a 30 μL aliquot of stool homogenate or plasma. Samples were vortexed and then centrifuged (10 min, 9,000 x g, 4°C) to pellet protein precipitates. Supernatants were transferred to glass autosampler vials containing inserts for LC-MS analysis.

Combined analysis:

Analysis ID AN004033 AN004034 AN004035 AN004036
Analysis type MS MS MS MS
Chromatography type HILIC Reversed phase HILIC Reversed phase
Chromatography system Shimadzu Nexera X2 Shimadzu Nexera X2 Shimadzu Nexera X2 Shimadzu Nexera X2
Column Waters Atlantis HILIC (150 x 2 mm, 3 µm) Waters Acquity BEH C8 (100 x 2.1mm, 1.7um) Phenomenex Luna NH2 (150 x 2.1mm, 3um) Waters ACQUITY UPLC BEH C18 (150 x 1.7mm,2.1um)
MS Type ESI ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Plus Orbitrap Thermo Q Exactive Plus Orbitrap Thermo Q Exactive Plus Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE POSITIVE NEGATIVE NEGATIVE
Units Abundance Abundance Abundance Abundance

Chromatography:

Chromatography ID:CH002981
Instrument Name:Shimadzu Nexera X2
Column Name:Waters Atlantis HILIC (150 x 2 mm, 3 µm)
Column Temperature:30C
Flow Gradient:Isocratically with 5% mobile phase A for 1 minute followed by a linear gradient to 40% mobile phase B over 10 minutes
Flow Rate:250 µL/min
Solvent A:100% water; 10 mM ammonium formate; 0.1% formic acid
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:HILIC
  
Chromatography ID:CH002982
Instrument Name:Shimadzu Nexera X2
Column Name:Waters Acquity BEH C8 (100 x 2.1mm, 1.7um)
Column Temperature:40C
Flow Gradient:The column was eluted at a flow rate of 450 µL/min isocratically for 1 minute at 80% mobile phase A, followed by a linear gradient to 80% mobile-phase B over 2 minutes, a linear gradient to 100% mobile phase B over 7 minutes, and then 3 minutes at 100% mobile-phase B.
Flow Rate:450 µL/min
Solvent A:95% water/5% methanol; 10 mM ammonium acetate; 0.1% acetic acid
Solvent B:100% methanol; 0.1% acetic acid
Chromatography Type:Reversed phase
  
Chromatography ID:CH002983
Instrument Name:Shimadzu Nexera X2
Column Name:Phenomenex Luna NH2 (150 x 2.1mm, 3um)
Column Temperature:30C
Flow Gradient:The column was eluted with initial conditions of 10% mobile phase A and 90% mobile phase B followed by a 10 min linear gradient to 100% mobile phase A.
Flow Rate:400 µL/min
Solvent A:100% water; 20 mM ammonium acetate; 20 mM ammonium hydroxide
Solvent B:75% acetonitrile/25% methanol; 10 mM ammonium hydroxide
Chromatography Type:HILIC
  
Chromatography ID:CH002984
Instrument Name:Shimadzu Nexera X2
Column Name:Waters ACQUITY UPLC BEH C18 (150 x 1.7mm,2.1um)
Column Temperature:45C
Flow Gradient:The column was eluted isocratically at a flow rate of 450 µL/min with 20% mobile phase A for 3 minutes followed by a linear gradient to 100% mobile phase B over 12 minutes.
Flow Rate:450 µL/min
Solvent A:100% water; 0.01% formic acid
Solvent B:100% acetonitrile; 0.01% acetic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS003780
Analysis ID:AN004033
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Raw data were processed using TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were confirmed using authentic reference standards or reference samples.
Ion Mode:POSITIVE
  
MS ID:MS003781
Analysis ID:AN004034
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Raw data were processed using TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were confirmed using authentic reference standards or reference samples.
Ion Mode:POSITIVE
  
MS ID:MS003782
Analysis ID:AN004035
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Raw data were processed using TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were confirmed using authentic reference standards or reference samples.
Ion Mode:NEGATIVE
  
MS ID:MS003783
Analysis ID:AN004036
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Raw data were processed using TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were confirmed using authentic reference standards or reference samples.
Ion Mode:NEGATIVE
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