Summary of Study ST002470

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 IDST002470
Study TitleLinking bacterial metabolites to disease-associated microbes to uncover mechanisms of host-microbial interactions in intestinal inflammation. Human plasma 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 Date2023-02-07
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:SU002560
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id collectionWeek PUCAI_C3_WKall
SA247519110890 mild
SA247520101910 mild
SA247521105750 mild
SA247522108770 mild
SA247523108960 mild
SA247524108110 mild
SA247525101770 mild
SA247526107620 mild
SA247527101800 mild
SA247528102790 mild
SA247529104050 moderate/severe
SA247530105900 moderate/severe
SA247531107930 moderate/severe
SA247532111220 moderate/severe
SA247533108360 moderate/severe
SA247534109560 moderate/severe
SA247535110410 moderate/severe
SA247536102400 moderate/severe
SA247537108840 moderate/severe
SA247538100220 moderate/severe
SA247539105620 moderate/severe
SA247540110570 moderate/severe
SA247541110800 moderate/severe
SA247542109150 moderate/severe
SA247543110730 moderate/severe
SA247544110210 moderate/severe
SA247545110400 moderate/severe
SA247546107050 moderate/severe
SA247547105040 moderate/severe
SA247548100370 moderate/severe
SA247549104580 moderate/severe
SA247550101260 moderate/severe
SA247551102630 moderate/severe
SA247552106030 moderate/severe
SA2475532063012 inactive
SA2475542052212 inactive
SA2475552046112 inactive
SA2475562027612 inactive
SA2475572065312 inactive
SA2475582018512 inactive
SA2475592048112 inactive
SA2475602063112 inactive
SA2475612037812 inactive
SA2475622029212 inactive
SA2475632013612 inactive
SA2475642064412 inactive
SA2475652001412 inactive
SA2475662049712 inactive
SA2475672031612 inactive
SA2475682011712 inactive
SA2475692011212 inactive
SA2475702067212 inactive
SA2475712064812 mild
SA2475722065412 mild
SA2475734055412 mild
SA2475744059312 mild
SA2475752018412 moderate/severe
SA2475762053912 moderate/severe
SA247577400014 inactive
SA247578400174 inactive
SA247579400664 inactive
SA247580402804 inactive
SA247581405214 inactive
SA247582401804 inactive
SA247583402294 inactive
SA247584400404 inactive
SA247585406734 inactive
SA247586407014 inactive
SA247587401774 inactive
SA247588404874 inactive
SA247589405354 inactive
SA247590405714 inactive
SA247591400144 mild
SA247592407204 mild
SA247593405954 mild
SA247594405394 mild
SA247595407164 mild
SA247596405114 mild
SA247597406264 mild
SA247598406914 mild
SA247599402444 mild
SA247600404374 mild
SA247601405554 mild
SA247602406354 moderate/severe
SA247603404554 moderate/severe
SA2476045016052 inactive
SA2476055052052 inactive
SA2476065042552 moderate/severe
SA2476075031552 moderate/severe
Showing results 1 to 89 of 89

Collection:

Collection ID:CO002553
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). Blood samples were collected Monday-Thursday and shipped on the same day (via FedEx overnight) at room temperature for next day delivery and processing by the biorepository. If samples were collected on Friday, blood tubes were stored at the collection site at 4 degrees and then shipped at room temperature on Monday (via FedEx overnight) for next day delivery and processing. Once samples were received by the Emory Biorepository, blood samples were immediately processed using the corresponding blood tube centrifugation guidelines, aliquoted, and stored at -80 degrees. Two types of blood tubes (Becton-Dickinson) were used for collection. One tube was coated with K2EDTA anticoagulant and proprietary protease inhibitor cocktail for stabilization of human plasma proteins at the point of collection. The second tube was also coated with K2EDTA anticoagulant.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR002572
Treatment Summary:NA

Sample Preparation:

Sampleprep ID:SP002566
Sampleprep Summary:LC-MS samples were prepared for four profiling methods from plasma samples 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 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 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 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 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 AN004029 AN004030 AN004031 AN004032
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:CH002977
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:CH002978
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:CH002979
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:CH002980
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:MS003776
Analysis ID:AN004029
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:MS003777
Analysis ID:AN004030
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:MS003778
Analysis ID:AN004031
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:MS003779
Analysis ID:AN004032
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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