Summary of Study ST002945
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.
Study ID | ST002945 |
Study Title | Polar fecal metabolomics of a patient cohort |
Study Type | (un)targeted MS |
Study Summary | This 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 b. polar fecal metabolomics of a patient cohort |
Institute | Ghent University |
Department | Department of Translational Physiology, Infectiology and Public Health |
Laboratory | Laboratory for Integrative Metabolomics |
Last Name | De Paepe |
First Name | Ellen |
Address | Salisburylaan 133, 9820 Merelbeke, Belgium |
Ellen.DePaepe@UGent.be | |
Phone | 0032479081098 |
Submit Date | 2023-07-06 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2023-11-01 |
Release Version | 1 |
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: | SU003058 |
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 |
---|---|---|
SA320704 | 15iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320705 | 16iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320706 | 1iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320707 | 14iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320708 | 13iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320709 | 10iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320710 | 12iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320711 | 2iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320712 | 11iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320713 | 8iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320714 | 3iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320715 | 7iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320716 | 9iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320717 | 6iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320718 | 4iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320719 | 5iQC | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320720 | 56 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320721 | 68 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320722 | 65 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320723 | 51 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320724 | 45 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320725 | 81 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320726 | 49 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320727 | 54 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320728 | 112 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320729 | 130 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320730 | 43 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320731 | 116 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320732 | 113 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320733 | 108 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320734 | 109 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320735 | 104 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320736 | 60 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320737 | 38 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320738 | 4 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320739 | 3 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320740 | 22 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320741 | 27 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320742 | 40 | 0 | IgE-other:0 | non-IgE CMA:0 | Healthy:1 |
SA320743 | 80 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320744 | 78 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320745 | 25 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320746 | 20 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320747 | 31 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320748 | 127 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320749 | 123 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320750 | 42 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320751 | 92 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320752 | 91 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320753 | 79 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320754 | 14 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320755 | 10 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320756 | 41 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320757 | 7 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320758 | 37 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320759 | 64 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320760 | 35 | 0 | IgE-other:0 | non-IgE CMA:1 | Healthy:0 |
SA320761 | 52 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320762 | 99 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320763 | 1 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320764 | 5 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320765 | 70 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320766 | 44 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320767 | 115 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320768 | 96 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320769 | 97 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320770 | 8 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320771 | 12 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320772 | 32 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320773 | 73 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320774 | 58 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320775 | 82 | 0 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320776 | 18 | 0 | IgE-other:1 | non-IgE CMA:1 | Healthy:0 |
SA320777 | 34 | 0 | IgE-other:1 | non-IgE CMA:1 | Healthy:0 |
SA320778 | 6 | 0 | IgE-other:1 | non-IgE CMA:1 | Healthy:0 |
SA320779 | 136 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320780 | 24 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320781 | 9 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320782 | 86 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320783 | 36 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320784 | 53 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320785 | 2 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320786 | 39 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320787 | 57 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320788 | 84 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320789 | 26 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320790 | 29 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320791 | 30 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320792 | 85 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320793 | 128 | 1 | IgE-other:0 | non-IgE CMA:0 | Healthy:0 |
SA320794 | 95 | 1 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320795 | 59 | 1 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320796 | 50 | 1 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320797 | 72 | 1 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320798 | 28 | 1 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320799 | 21 | 1 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
SA320800 | 16 | 1 | IgE-other:1 | non-IgE CMA:0 | Healthy:0 |
Showing results 1 to 97 of 97 |
Collection:
Collection ID: | CO003051 |
Collection Summary: | Fecal samples were collected through spontaneous defecation in the diaper or using a Fecotainer® (AT Medical B.V., Enschede, The Netherlands). Samples were stored at -20 °C until pick-up (< 1 week). Following cooled transport (dry ice or icepacks), fecal samples were briefly stored at -80 °C, lyophilized, and homogenized in preparation for more long-term storage at -80 °C. |
Sample Type: | Feces |
Collection Method: | Spontaneous defecation |
Storage Conditions: | -80℃ |
Treatment:
Treatment ID: | TR003067 |
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: | SP003064 |
Sampleprep Summary: | To extract the polar fecal metabolome, 200 mg of lyophilized homogenized feces was dissolved in 4 mL of ultrapure water, after the addition of 100 mL ISTD mixture (25 ng mL&1 of Dvaline- d8 and L-alanine-d3). Subsequent to 30 s of thorough vortexing, 1 mL of an ice-cold methanol and ultrapure water (80:20, v/ v) mixture was added. The supernatant of the solid-liquid extraction was collected after 1 min of vortexing and 10 min of rotation, followed by a 10-min centrifugation step (13 300 x g, at 4 %C). Next, the extract was passed over a polyamide filter (diameter of 25mm and pore size of 0.45 mm) (Machery-Nagel, Düren, Germany), diluted (1:3) with ultrapure water and transferred to a glass HPLCvial. |
Sampleprep Protocol ID: | De_Paepe_et_al_2018.pdf |
Processing Storage Conditions: | -80℃ |
Sample Spiking: | Internal standard |
Combined analysis:
Analysis ID | AN004830 |
---|---|
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: | CH003650 |
Methods Filename: | De_Paepe_et_al_2018.pdf |
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: 0e1.5 min at 98%, 1.5e7.0 min from 98% to 75%, 7.0e8.0 min from 75% to 40%, 8.0e12.0 min from 40% to 5%, 12.0e14.0 min at 5%, 14.0e14.1 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: | MS004576 |
Analysis ID: | AN004830 |
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: | UNSPECIFIED |
Analysis Protocol File: | De_Paepe_et_al_2018.pdf |