Summary of project PR001831
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
| 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 |
Summary of all studies in project PR001831
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002944 | Longitudinal polar fecal metabolomics of mice undergoing sensitization to beta-lactoglobulin | Mus musculus | Ghent University | MS* | 2023-11-01 | 1 | 329 | Uploaded data (21.5G)* |
| ST002945 | Polar fecal metabolomics of a patient cohort | Homo sapiens | Ghent University | MS* | 2023-11-01 | 1 | 97 | Uploaded data (7.6G)* |
| ST002946 | Fecal lipidomics of a patient cohort | Homo sapiens | Ghent University | MS* | 2023-11-01 | 1 | 97 | Uploaded data (4.6G)* |
| ST002985 | Polar metabolomics of in vitro digestions of commercial cow's milk formula. | Homo sapiens | Ghent University | MS* | 2023-11-29 | 1 | 124 | Uploaded data (12.7G)* |
| ST002988 | Polar urinary metabolomics of a patient cohort | Homo sapiens | Ghent University | MS* | 2023-11-29 | 1 | 90 | Uploaded data (6.6G)* |
