Summary of Study ST002944

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.

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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 IDST002944
Study TitleLongitudinal polar fecal metabolomics of mice undergoing sensitization to beta-lactoglobulin
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 a. longitudinal polar fecal metabolomics of mice undergoing sensitization to beta-lactoglobulin
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 Date2023-07-06
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-11-01
Release Version1
Ellen De Paepe Ellen De Paepe
https://dx.doi.org/10.21228/M81Q73
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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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
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