Summary of Study ST002988

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 PR001831. The data can be accessed directly via it's Project DOI: 10.21228/M81Q73 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 IDST002988
Study TitlePolar urinary metabolomics of a patient cohort
Study Type(un)targeted MS
Study SummaryThis study is part of a multi-part study, including a. longitudinal polar fecal metabolomics of mice undergoing sensitization to beta-lactoglobulin b. polar fecal metabolomics of a patient cohort c. fecal lipidomics of a patient cohort d. polar urinary metabolomics of a patient cohort e. polar metabolomics of in vitro digestions This specific part is part d. polar urinary metabolomics of a patient cohort
Institute
Ghent University
DepartmentDepartment of Translational Physiology, Infectiology and Public Health
LaboratoryLaboratory for Integrative Metabolomics
Last NameDe Paepe
First NameEllen
AddressSalisburylaan 133, 9820 Merelbeke, Belgium
EmailEllen.DePaepe@UGent.be
Phone0032479081098
Submit Date2023-07-07
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-11-29
Release Version1
Ellen De Paepe Ellen De Paepe
https://dx.doi.org/10.21228/M81Q73
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001831
Project DOI:doi: 10.21228/M81Q73
Project Title:Integrated gut metabolome and microbiome fingerprinting reveals that dysbiosis precedes allergic inflammation in IgE-mediated pediatric cow’s milk allergy
Project Type:(un)targeted MS
Project Summary:Background: IgE-mediated cow’s milk allergy (IgE-CMA) is one of the first allergies to arise in early childhood and may result from exposure to various milk allergens, of which β-lactoglobulin (BLG) and casein are the most important. Understanding the underlying mechanisms behind IgE-CMA is imperative for the discovery of novel biomarkers and the design of innovative treatment and prevention strategies. Methods: We report a longitudinal in vivo murine model, in which 2 mice strains (BALB/c and C57Bl/6) were sensitized to BLG using either cholera toxin or an oil emulsion (n=6 per group). After sensitization, mice were challenged orally, their clinical signs monitored, antibody (IgE and IgG1) and cytokine levels (IL-4 and IFN-γ) measured, and fecal samples subjected to metabolomics. The results of the murine models were further supported by fecal microbiome-metabolome data from our population of IgE-CMA (n=24) and healthy (n=23) children (Trial: NCT04249973), on which polar metabolomics, lipidomics and 16S rRNA metasequencing were performed. In vitro gastrointestinal digestions and multi-omics corroborated the microbial origin of proposed metabolic changes. Results: During sensitization, we observed multiple microbially derived metabolic alterations, most importantly bile acid, energy and tryptophan metabolites, that preceded allergic inflammation. The latter was reflected in a disturbed sphingolipid metabolism. We confirmed microbial dysbiosis, and its causal effect on metabolic alterations in our patient cohort, which was accompanied by metabolic signatures of low-grade inflammation. Conclusion: Our results indicate that gut dysbiosis precedes allergic inflammation and nurtures a chronic low-grade inflammation in children on elimination diets, opening important new opportunities for future prevention and treatment strategies.
Institute:Ghent University
Department:Translational Physiology, Infectiology and Public Health
Laboratory:Laboratory for Integrative Metabolomics
Last Name:De Paepe
First Name:Ellen
Address:Salisburylaan 133, Merelbeke, Oost-Vlaanderen, 9820, Belgium
Email:Ellen.DePaepe@UGent.be
Phone:0032479081098
Funding Source:Fonds Wetenschappelijk Onderzoek

Subject:

Subject ID:SU003101
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:< 5 years old
Gender:Male and female

Factors:

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

mb_sample_id local_sample_id IgE CMA IgE other non-IgE CMA Healthy
SA325660iQC150 0 0 0
SA325661iQC160 0 0 0
SA325662iQC20 0 0 0
SA325663iQC140 0 0 0
SA325664iQC120 0 0 0
SA325665iQC100 0 0 0
SA325666iQC110 0 0 0
SA325667iQC30 0 0 0
SA325668iQC130 0 0 0
SA325669iQC10 0 0 0
SA325670iQC40 0 0 0
SA325671iQC90 0 0 0
SA325672iQC70 0 0 0
SA325673iQC80 0 0 0
SA325674iQC60 0 0 0
SA325675iQC50 0 0 0
SA325676810 0 0 1
SA325677430 0 0 1
SA325678400 0 0 1
SA325679450 0 0 1
SA3256801040 0 0 1
SA325681540 0 0 1
SA325682650 0 0 1
SA325683680 0 0 1
SA3256841080 0 0 1
SA325685510 0 0 1
SA325686490 0 0 1
SA3256871120 0 0 1
SA32568830 0 0 1
SA3256891090 0 0 1
SA325690270 0 0 1
SA32569140 0 0 1
SA325692220 0 0 1
SA3256931300 0 0 1
SA325694600 0 0 1
SA3256951160 0 0 1
SA3256961130 0 0 1
SA325697780 0 1 0
SA325698920 0 1 0
SA325699790 0 1 0
SA3257001230 0 1 0
SA325701800 0 1 0
SA3257021270 0 1 0
SA325703640 0 1 0
SA325704310 0 1 0
SA325705250 0 1 0
SA325706420 0 1 0
SA325707350 0 1 0
SA325708390 0 1 0
SA325709370 0 1 0
SA325710410 0 1 0
SA325711200 0 1 0
SA325712100 0 1 0
SA325713140 0 1 0
SA32571470 0 1 0
SA32571550 1 0 0
SA32571680 1 0 0
SA32571710 1 0 0
SA325718120 1 0 0
SA325719320 1 0 0
SA3257201150 1 0 0
SA325721440 1 0 0
SA325722730 1 0 0
SA325723520 1 0 0
SA325724580 1 0 0
SA325725700 1 0 0
SA325726960 1 0 0
SA325727340 1 1 0
SA325728180 1 1 0
SA32572960 1 1 0
SA325730970 2 0 0
SA325731990 2 0 0
SA325732241 0 0 0
SA325733571 0 0 0
SA32573421 0 0 0
SA325735531 0 0 0
SA325736261 0 0 0
SA325737841 0 0 0
SA325738851 0 0 0
SA325739861 0 0 0
SA325740361 0 0 0
SA325741301 0 0 0
SA3257421281 0 0 0
SA3257431361 0 0 0
SA325744291 0 0 0
SA325745211 1 0 0
SA325746591 1 0 0
SA325747951 1 0 0
SA325748281 1 0 0
SA325749161 1 0 0
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Collection:

Collection ID:CO003094
Collection Summary:Urine samples were collected using The Newcastle Urine Collector (SteriSets Medical Products, Guilhufe, Portugal) or directly in a plastic container. Samples were stored at -20 °C until pick-up (< 1 week). Following cooled transport (dry ice or icepacks). Urine samples were thawed and aliquoted upon arrival and stored at -80 °C awaiting analysis.
Sample Type:Urine
Collection Method:Spontaneous defecation
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003110
Treatment Summary:No treatment was applied, patients were divided into 4 different control groups: - IgE-mediated cow's milk allergy - other functional gastrointestinal disorder - IgE-mediated other food allergy - healthy brothers and sisters

Sample Preparation:

Sampleprep ID:SP003107
Sampleprep Summary:Extraction of the urinary metabolome was initiated by pipetting 300 mL urine into a 1.5-mL Eppendorf tube, after which 30 mL of ISTD mixture (100 ng mL&1 D-valine-d8 and of L-alanine-d3) was added. Following this, the sample was centrifuged for 8 min (1 000 x g, 4 %C). Next, 100 mL supernatant was collected and diluted (1:10) with ultrapure water, after which the resulting extract was transferred to a glass HPLC-vial.
Processing Storage Conditions:-80℃
Sample Spiking:Internal standard

Combined analysis:

Analysis ID AN004908
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Dionex Ultimate 3000
Column Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode UNSPECIFIED
Units a.u.

Chromatography:

Chromatography ID:CH003703
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um)
Column Temperature:45
Flow Gradient:A gradient profile with following proportions (v/v) of solvent A was applied: 0-1.5 min at 98%, 1.5-7.0 min from 98% to 75%, 7.0-8.0 min from 75% to 40%, 8.0-12.0 min from 40% to 5%, 12.0-14.0 min at 5%, 14.0-14.1 min from 5 to 98%, followed by 4.0 min of re-equilibration.
Flow Rate:0.4 mL/min
Internal Standard:L-alanine-d3, D-valine-d8
Sample Injection:10 uL
Solvent A:100% water; 0.1% formic acid
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS004651
Analysis ID:AN004908
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS acquisition: Xcalibur Targeted data processing: Xcalibur Untargeted data acquisition: Compound Discoverer, R studio Ion mode is unspecified as analysis is performed in polarity switching mode, thereby generating data for both positive and negative ionization at the same time.
Ion Mode:UNSPECIFIED
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