Summary of Study ST004370

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 PR002768. The data can be accessed directly via it's Project DOI: 10.21228/M8VR9N This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study IDST004370
Study TitleMedium chain triglycerides induce metabolic shifts in dogs with idiopathic epilepsy: a multi-omics approach - fecal metabolome
Study TypeDouble-blinded placebo controlled dietary trial in dogs - Fecal metabolome
Study SummaryFecal metabolome dataset - Background: Medium chain triglycerides (MCT) are a class of dietary lipids with proposed beneficial health effects in animals and humans alike. Their mechanism of action in specific applications, like epilepsy, remains however unclear. Therefore, the aim of this study was to identify alterations in the fecal and plasma metabolome and fecal microbiome in dogs with idiopathic epilepsy (IE) following an MCT diet. A double-blinded placebo controlled dietary trial including 32 dogs with drug-resistant IE was established. Dogs were randomly allocated to an MCT (n = 16) or placebo diet (n = 16) for 3 months. Feces and plasma were collected at the start and end of the dietary trial. The metabolome of plasma and feces were analysed using liquid chromatography coupled to high resolution mass spectrometry, and the fecal bacterial phylogeny was examined using 16S rRNA sequencing. Fecal metabolome, plasma metabolome and fecal microbiome data were integrated using the DIABLO framework. Results: The MCT diet elicited distinct metabolic adaptations and modulated gut microbial composition, notably characterized by alterations in histidine and energy metabolism, a reduction in Escherichia-Shigella, and an enrichment of genera including Ruminococcus and Faecalitalea. Multiple correlations were observed between significantly altered microbial taxa and fecal metabolites like e.g. 1-methylhistidine and creatine. Conclusion: Our findings demonstrate that a diet rich in MCT does not only support peripheral energy metabolism, evidenced by stable carnitine metabolites and reduced plasma threonine, but also reshapes microbial composition. Therefore, potential involvement of the microbiota–gut–brain axis in the mechanism of action for MCT in dogs with IE was underscored.
Institute
Ghent University
DepartmentDI11 - DI04
LaboratoryECAN - LIMET
Last NameVerdoodt
First NameFien
AddressSalisburylaan 133
Emailfien.verdoodt@ugent.be
Phone+32476076770
Submit Date2025-11-14
Num Groups2
Total Subjects32
Num Males20
Num Females12
Study CommentsMCT vs placebo
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2025-12-15
Release Version1
Fien Verdoodt Fien Verdoodt
https://dx.doi.org/10.21228/M8VR9N
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002768
Project DOI:doi: 10.21228/M8VR9N
Project Title:Medium chain triglycerides induce metabolic shifts in dogs with idiopathic epilepsy: a multi-omics approach
Project Type:Double blinded placebo-controlled dietary trial in dogs with idiopathic epilepsy
Project Summary:Background: Medium chain triglycerides (MCT) are a class of dietary lipids with proposed beneficial health effects in animals and humans alike. Their mechanism of action in specific applications, like epilepsy, remains however unclear. Therefore, the aim of this study was to identify alterations in the fecal and plasma metabolome and fecal microbiome in dogs with idiopathic epilepsy (IE) following an MCT diet. A double-blinded placebo controlled dietary trial including 32 dogs with drug-resistant IE was established. Dogs were randomly allocated to an MCT (n = 16) or placebo diet (n = 16) for 3 months. Feces and plasma were collected at the start and end of the dietary trial. The metabolome of plasma and feces were analysed using liquid chromatography coupled to high resolution mass spectrometry, and the fecal bacterial phylogeny was examined using 16S rRNA sequencing. Fecal metabolome, plasma metabolome and fecal microbiome data were integrated using the DIABLO framework. Results: The MCT diet elicited distinct metabolic adaptations and modulated gut microbial composition, notably characterized by alterations in histidine and energy metabolism, a reduction in Escherichia-Shigella, and an enrichment of genera including Ruminococcus and Faecalitalea. Multiple correlations were observed between significantly altered microbial taxa and fecal metabolites like e.g. 1-methylhistidine and creatine. Conclusion: Our findings demonstrate that a diet rich in MCT does not only support peripheral energy metabolism, evidenced by stable carnitine metabolites and reduced plasma threonine, but also reshapes microbial composition. Therefore, potential involvement of the microbiota–gut–brain axis in the mechanism of action for MCT in dogs with IE was underscored.
Institute:Ghent University
Department:DI11 - DI04
Laboratory:ECAN - LIMET
Last Name:Verdoodt
First Name:Fien
Address:Salisburylaan 133, Merelbeke, Flanders, 9820, Belgium
Email:fien.verdoodt@ugent.be
Phone:+32476076770
Funding Source:FWO
Publications:Preprint available at https://doi.org/10.21203/rs.3.rs-8078706/v1

Subject:

Subject ID:SU004529
Subject Type:Mammal
Subject Species:Canis lupus familiaris
Taxonomy ID:9615
Age Or Age Range:1-10 years old
Weight Or Weight Range:5.1-52.4 kg
Gender:Male and female
Animal Animal Supplier:pets
Animal Housing:at home (pets)
Animal Feed:MCT-diet or isocaloric placebo diet
Animal Inclusion Criteria:idiopathic epilepsy Tier I (IVETF)

Factors:

Subject type: Mammal; Subject species: Canis lupus familiaris (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Diet Timepoint
SA519837Dog1T0Feces MCT 0
SA519838Dog29T0Feces MCT 0
SA519839Dog8T0Feces MCT 0
SA519840Dog18T0Feces MCT 0
SA519841Dog27T0Feces MCT 0
SA519842Dog37T0Feces MCT 0
SA519843Dog38T0Feces MCT 0
SA519844Dog20T0Feces MCT 0
SA519845Dog12T0Feces MCT 0
SA519846Dog10T0Feces MCT 0
SA519847Dog19T0Feces MCT 0
SA519848Dog25T0Feces MCT 0
SA519849Dog35T0Feces MCT 0
SA519850Dog11T0Feces MCT 0
SA519851Dog16T0Feces MCT 0
SA519852Dog7T0Feces MCT 0
SA519853Dog11T3Feces MCT 3
SA519854Dog1T3Feces MCT 3
SA519855Dog29T3Feces MCT 3
SA519856Dog16T3Feces MCT 3
SA519857Dog35T3Feces MCT 3
SA519858Dog37T3Feces MCT 3
SA519859Dog12T3Feces MCT 3
SA519860Dog19T3Feces MCT 3
SA519861Dog20T3Feces MCT 3
SA519862Dog27T3Feces MCT 3
SA519863Dog7T3Feces MCT 3
SA519864Dog25T3Feces MCT 3
SA519865Dog10T3Feces MCT 3
SA519866Dog38T3Feces MCT 3
SA519867Dog8T3Feces MCT 3
SA519868Dog18T3Feces MCT 3
SA519869Dog9T0Feces Placebo 0
SA519870Dog17T0Feces Placebo 0
SA519871Dog28T0Feces Placebo 0
SA519872Dog6T0Feces Placebo 0
SA519873Dog30T0Feces Placebo 0
SA519874Dog21T0Feces Placebo 0
SA519875Dog26T0Feces Placebo 0
SA519876Dog33T0Feces Placebo 0
SA519877Dog42T0Feces Placebo 0
SA519878Dog39T0Feces Placebo 0
SA519879Dog34T0Feces Placebo 0
SA519880Dog13T0Feces Placebo 0
SA519881Dog24T0Feces Placebo 0
SA519882Dog5T0Feces Placebo 0
SA519883Dog3T0Feces Placebo 0
SA519884Dog4T0Feces Placebo 0
SA519885Dog30T3Feces Placebo 3
SA519886Dog42T3Feces Placebo 3
SA519887Dog21T3Feces Placebo 3
SA519888Dog6T3Feces Placebo 3
SA519889Dog33T3Feces Placebo 3
SA519890Dog9T3Feces Placebo 3
SA519891Dog17T3Feces Placebo 3
SA519892Dog4T3Feces Placebo 3
SA519893Dog13T3Feces Placebo 3
SA519894Dog5T3Feces Placebo 3
SA519895Dog34T3Feces Placebo 3
SA519896Dog28T3Feces Placebo 3
SA519897Dog24T3Feces Placebo 3
SA519898Dog26T3Feces Placebo 3
SA519899Dog39T3Feces Placebo 3
SA519900Dog3T3Feces Placebo 3
SA519901QC91pool - -
SA519902QC101pool - -
SA519903QC93pool - -
SA519904QC71pool - -
SA519905QC83pool - -
SA519906QC81pool - -
SA519907QC73pool - -
SA519908QC111pool - -
SA519909QC63pool - -
SA519910QC103pool - -
SA519911QC52pool - -
SA519912QC12pool - -
SA519913QC22pool - -
SA519914QC32pool - -
SA519915QC42pool - -
SA519916QC62pool - -
SA519917QC72pool - -
SA519918QC82pool - -
SA519919QC92pool - -
SA519920QC102pool - -
SA519921QC112pool - -
SA519922QC61pool - -
SA519923QC53pool - -
SA519924QC51pool - -
SA519925QC04pool - -
SA519926QC43pool - -
SA519927QC01pool - -
SA519928QC02pool - -
SA519929QC03pool - -
SA519930QC11pool - -
SA519931QC13pool - -
SA519932QC21pool - -
SA519933QC23pool - -
SA519934QC31pool - -
SA519935QC33pool - -
SA519936QC41pool - -
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Collection:

Collection ID:CO004522
Collection Summary:Freshly voided fecal samples were collected at T0 and T3, within 15 minutes, frozen, and stored at -20°C for a maximum of 24 h at home by the owners until cooled transport. After arrival at the research facility, fecal samples were aliquoted for DNA extraction and 16S rRNA sequencing (stored at -20°C), and metabolome analysis (stored at -80°C). Fecal aliquots for metabolome analysis were subjected to 72 h of lyophilization to facilitate homogenization. T0 = Before the start of the placebo-controlled dietary trial. All dogs did receive an identical, adult maintenance diet for at least 21 days before the collection of T0 samples. T3 = At the end of the placebo-controlled dietary trial, i.e. following 3 months on either placebo or medium chain triglycerides (MCT) diet. (NOTE: Fe=female entire, Fs=female spayed, Ma=male intact, Ms=male neutered; BCS=body condition score 1-9)
Sample Type:Feces
Collection Method:Collected by owner and frozen within 15 minutes
Collection Location:Belgium - at home dog owners
Collection Frequency:twice per dog (T0 and T3)
Storage Conditions:-80℃

Treatment:

Treatment ID:TR004538
Treatment Summary:Medium chain triglyceride diet OR isocaloric placebo diet (containing long chain triglycerides)

Sample Preparation:

Sampleprep ID:SP004535
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 25 µL ISTD mixture (100 ng/µl of tyrosine-d2, phenylalanine-d2, deoxycholic acid-d4, l-alanine-d3 and dopamine-d4). 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℃
Extract Storage:4℃
Sample Spiking:ISTD

Combined analysis:

Analysis ID AN007300 AN007301
Chromatography ID CH005542 CH005542
MS ID MS006994 MS006995
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Dionex Ultimate 3000 Thermo Dionex Ultimate 3000
Column Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um) Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode NEGATIVE POSITIVE
Units iQC normalized AUC iQC normalized AUC

Chromatography:

Chromatography ID:CH005542
Chromatography Summary:Reversed phase Chromatography
Methods ID:CH003650
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
Solvent A:100% water; 0.1% formic acid
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS006994
Analysis ID:AN007300
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS acquisition: Xcalibur, polarity switching mode, according to De Paepe et al, 2018 Targeted data processing: TARDIS Untargeted data acquisition: Compound Discoverer, R studio
Ion Mode:NEGATIVE
Capillary Voltage:90 V
Ionization:Negative
Spray Voltage:- 5 kV
  
MS ID:MS006995
Analysis ID:AN007301
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS acquisition: Xcalibur, polarity switching mode, according to De Paepe et al, 2018 Targeted data processing: TARDIS Untargeted data acquisition: Compound Discoverer, R studio
Ion Mode:POSITIVE
Capillary Voltage:90 V
Ionization:Positive
Spray Voltage:+ 5 kV
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