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.

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 ID	ST002944
Study Title	Longitudinal polar fecal metabolomics of mice undergoing sensitization to beta-lactoglobulin
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 a. longitudinal polar fecal metabolomics of mice undergoing sensitization to beta-lactoglobulin
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
Email	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:	SU003057
Subject Type:	Mammal
Subject Species:	Mus musculus
Taxonomy ID:	10090
Genotype Strain:	BALB/c and C57Bl/6
Age Or Age Range:	3-10 weeks
Gender:	Female
Animal Animal Supplier:	Charles River
Animal Housing:	SPF
Animal Feed:	Sniff
Animal Water:	Ad libitum

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id	local_sample_id	Strain	treatment	week
SA320431	S_21_0066_35	B6	1A	Wk 1
SA320432	S_21_0066_191	B6	1A	Wk 4
SA320433	S_21_0066_179	B6	1B	Wk 4
SA320434	S_21_0066_129	B6	1C	Wk 1
SA320435	S_21_0066_205	B6	1C	Wk 4
SA320436	S_21_0066_75	B6	1D	Wk 4
SA320437	S_21_0066_125	B6	1E	Wk 1
SA320438	S_21_0066_34	B6	1E	Wk 4
SA320439	S_21_0066_31	B6	1F	Wk 1
SA320440	S_21_0066_124	B6	1F	Wk 4
SA320441	S_21_0066_16	B6	1W	Wk 1
SA320442	S_21_0066_190	B6	1X	Wk 1
SA320443	S_21_0066_273	B6	1X	Wk 7
SA320444	S_21_0066_245	B6	1Y	Wk 7
SA320445	S_21_0066_308	B6	1Z	Wk 1
SA320446	S_21_0066_236	B6	1Z	Wk 7
SA320447	S_21_0066_267	B6	2A	Wk 1
SA320448	S_21_0066_93	B6	2A	Wk 4
SA320449	S_21_0066_195	B6	2B	Wk 4
SA320450	S_21_0066_211	B6	2C	Wk 1
SA320451	S_21_0066_193	B6	2C	Wk 4
SA320452	S_21_0066_8	B6	2D	Wk 4
SA320453	S_21_0066_86	B6	2E	Wk 1
SA320454	S_21_0066_158	B6	2E	Wk 4
SA320455	S_21_0066_23	B6	2F	Wk 4
SA320456	S_21_0066_126	B6	2W	Wk 1
SA320457	S_21_0066_263	B6	2X	Wk 1
SA320458	S_21_0066_244	B6	2X	Wk 7
SA320459	S_21_0066_207	B6	2Y	Wk 7
SA320460	S_21_0066_260	B6	2Z	Wk 1
SA320461	S_21_0066_254	B6	3A	Wk 1
SA320462	S_21_0066_132	B6	3A	Wk 4
SA320463	S_21_0066_73	B6	3B	Wk 4
SA320464	S_21_0066_60	B6	3C	Wk 1
SA320465	S_21_0066_222	B6	3C	Wk 4
SA320466	S_21_0066_21	B6	3D	Wk 4
SA320467	S_21_0066_264	B6	3E	Wk 4
SA320468	S_21_0066_282	B6	3F	Wk 4
SA320469	S_21_0066_116	B6	3W	Wk 1
SA320470	S_21_0066_294	B6	3W	Wk 7
SA320471	S_21_0066_271	B6	3X	Wk 1
SA320472	S_21_0066_262	B6	3X	Wk 7
SA320473	S_21_0066_118	B6	3Z	Wk 1
SA320474	S_21_0066_41	B6	3Z	Wk 7
SA320475	S_21_0066_151	B6	4A	Wk 4
SA320476	S_21_0066_56	B6	4B	Wk 1
SA320477	S_21_0066_71	B6	4B	Wk 4
SA320478	S_21_0066_202	B6	4C	Wk 1
SA320479	S_21_0066_103	B6	4C	Wk 4
SA320480	S_21_0066_198	B6	4D	Wk 1
SA320481	S_21_0066_172	B6	4D	Wk 4
SA320482	S_21_0066_268	B6	4E	Wk 1
SA320483	S_21_0066_47	B6	4E	Wk 4
SA320484	S_21_0066_229	B6	4F	Wk 4
SA320485	S_21_0066_5	B6	4W	Wk 1
SA320486	S_21_0066_286	B6	4W	Wk 7
SA320487	S_21_0066_261	B6	4X	Wk 1
SA320488	S_21_0066_12	B6	4X	Wk 7
SA320489	S_21_0066_168	B6	4Y	Wk 1
SA320490	S_21_0066_13	B6	4Y	Wk 7
SA320491	S_21_0066_288	B6	4Z	Wk 7
SA320492	S_21_0066_252	B6	5A	Wk 1
SA320493	S_21_0066_233	B6	5A	Wk 4
SA320494	S_21_0066_62	B6	5B	Wk 1
SA320495	S_21_0066_184	B6	5B	Wk 4
SA320496	S_21_0066_102	B6	5C	Wk 1
SA320497	S_21_0066_101	B6	5C	Wk 4
SA320498	S_21_0066_55	B6	5D	Wk 1
SA320499	S_21_0066_20	B6	5D	Wk 4
SA320500	S_21_0066_58	B6	5E	Wk 1
SA320501	S_21_0066_209	B6	5E	Wk 4
SA320502	S_21_0066_50	B6	5F	Wk 1
SA320503	S_21_0066_206	B6	5F	Wk 4
SA320504	S_21_0066_274	B6	5W	Wk 1
SA320505	S_21_0066_311	B6	5W	Wk 7
SA320506	S_21_0066_36	B6	5X	Wk 1
SA320507	S_21_0066_174	B6	5X	Wk 7
SA320508	S_21_0066_37	B6	5Y	Wk 1
SA320509	S_21_0066_306	B6	5Y	Wk 7
SA320510	S_21_0066_287	B6	5Z	Wk 1
SA320511	S_21_0066_139	B6	5Z	Wk 7
SA320512	S_21_0066_61	B6	6A	Wk 1
SA320513	S_21_0066_53	B6	6A	Wk 4
SA320514	S_21_0066_80	B6	6B	Wk 4
SA320515	S_21_0066_18	B6	6C	Wk 1
SA320516	S_21_0066_266	B6	6C	Wk 4
SA320517	S_21_0066_128	B6	6D	Wk 1
SA320518	S_21_0066_28	B6	6D	Wk 4
SA320519	S_21_0066_279	B6	6E	Wk 1
SA320520	S_21_0066_57	B6	6E	Wk 4
SA320521	S_21_0066_51	B6	6F	Wk 1
SA320522	S_21_0066_214	B6	6F	Wk 4
SA320523	S_21_0066_54	B6	6W	Wk 1
SA320524	S_21_0066_199	B6	6W	Wk 7
SA320525	S_21_0066_32	B6	6X	Wk 1
SA320526	S_21_0066_68	B6	6X	Wk 7
SA320527	S_21_0066_215	B6	6Y	Wk 1
SA320528	S_21_0066_105	B6	6Y	Wk 7
SA320529	S_21_0066_304	B6	6Z	Wk 1
SA320530	S_21_0066_224	B6	6Z	Wk 7

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Collection:

Collection ID:	CO003050
Collection Summary:	Fecal samples were collected on different timepoints during sensitization of the mice. Samples were freeze-dried within one week after collection and stored at -80° awaiting analysis
Sample Type:	Feces
Collection Method:	Spontaneous defecation
Collection Frequency:	1x week
Storage Conditions:	-80℃

Treatment:

Treatment ID:	TR003066
Treatment Summary:	Two different mice strains and two different protocols were tested: BALB/c (BC) mice and C57Bl/6 (B6) mice. The first sensitization protocol was based on Adel-Patient et al., in which 4-week-old mice received oral gavages containing ß-lactoglobulin (BLG) and cholera toxin (CT) once a week for 6 weeks 20 (treatment W), the control groups received either BLG in PBS (X), CT in PBS (Y) or PBS alone (Z). The second protocol was adapted from Shindo et al. and included intragastrical administration of BLG in PBS or oil emulsion, followed by intraperitoneal injection of sodium salicylate (SA). The latter protocol was performed 5x a week for 3 weeks. Group A received BLG in PBS + SA, group B BLG in oil + SA, group C BLG in PBS + PBS, group D BLG in oil + PBS, group E and F were vehicle controls with group E receiving PBS + SA, and group F oil + SA
Treatment Compound:	Beta-lactoglobulin, cholera toxin
Treatment Route:	oral gavage, intraperitoneal injection
Treatment Dose:	1 mg ß-lactoglobulin (BLG) per g body weight mixed with 10 µg of cholera toxin (CT) in 0.1 mL PBS, or 1 mg BLG in 0.1 mL individual antigen solution (vehicle), which was either PBS or an oil emulsion (saline, linoleic acid, and lecithin at 5:4:1 by volume). Intraperitoneal administration of 0.1 mL PBS or PBS containing 0.2 mg sodium salicylate (SA)
Treatment Doseduration:	3 or 7 weeks
Treatment Vehicle:	PBS or oil emulsion
Animal Anesthesia:	CO
Animal Fasting:	Evening before antigen challenge
Animal Endp Euthanasia:	cervical dislocation
Animal Endp Clinical Signs:	severe anaphylaxis

Sample Preparation:

Sampleprep ID:	SP003063
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.
Processing Storage Conditions:	-80℃
Sample Spiking:	Internal standard

Combined analysis:

Analysis ID	AN004829
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:	CH003649
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:	MS004575
Analysis ID:	AN004829
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