Summary of Study ST004369

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 IDST004369
Study TitleMedium chain triglycerides induce metabolic shifts in dogs with idiopathic epilepsy: a multi-omics approach - plasma metabolome
Study TypeDouble-blinded placebo controlled dietary trial in dogs - Plasma metabolome
Study SummaryPlasma 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 Date2025-11-11
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:SU004528
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
SA519702Dog27T0plasma MCT 0
SA519703Dog18T0plasma MCT 0
SA519704Dog19T0plasma MCT 0
SA519705Dog20T0plasma MCT 0
SA519706Dog12T0plasma MCT 0
SA519707Dog11T0plasma MCT 0
SA519708Dog25T0plasma MCT 0
SA519709Dog10T0plasma MCT 0
SA519710Dog8T0plasma MCT 0
SA519711Dog7T0plasma MCT 0
SA519712Dog29T0plasma MCT 0
SA519713Dog35T0plasma MCT 0
SA519714Dog37T0plasma MCT 0
SA519715Dog38T0plasma MCT 0
SA519716Dog1T0plasma MCT 0
SA519717Dog16T0plasma MCT 0
SA519718Dog29T3plasma MCT 3
SA519719Dog18T3plasma MCT 3
SA519720Dog27T3plasma MCT 3
SA519721Dog25T3plasma MCT 3
SA519722Dog35T3plasma MCT 3
SA519723Dog37T3plasma MCT 3
SA519724Dog20T3plasma MCT 3
SA519725Dog19T3plasma MCT 3
SA519726Dog38T3plasma MCT 3
SA519727Dog1T3plasma MCT 3
SA519728Dog16T3plasma MCT 3
SA519729Dog12T3plasma MCT 3
SA519730Dog11T3plasma MCT 3
SA519731Dog7T3plasma MCT 3
SA519732Dog10T3plasma MCT 3
SA519733Dog8T3plasma MCT 3
SA519734Dog17T0plasma Pl 0
SA519735Dog39T0plasma Pl 0
SA519736Dog34T0plasma Pl 0
SA519737Dog5T0plasma Pl 0
SA519738Dog33T0plasma Pl 0
SA519739Dog30T0plasma Pl 0
SA519740Dog4T0plasma Pl 0
SA519741Dog28T0plasma Pl 0
SA519742Dog26T0plasma Pl 0
SA519743Dog6T0plasma Pl 0
SA519744Dog9T0plasma Pl 0
SA519745Dog24T0plasma Pl 0
SA519746Dog42T0plasma Pl 0
SA519747Dog21T0plasma Pl 0
SA519748Dog3T0plasma Pl 0
SA519749Dog13T0plasma Pl 0
SA519750Dog42T3plasma Pl 3
SA519751Dog39T3plasma Pl 3
SA519752Dog3T3plasma Pl 3
SA519753Dog17T3plasma Pl 3
SA519754Dog5T3plasma Pl 3
SA519755Dog4T3plasma Pl 3
SA519756Dog34T3plasma Pl 3
SA519757Dog21T3plasma Pl 3
SA519758Dog30T3plasma Pl 3
SA519759Dog6T3plasma Pl 3
SA519760Dog28T3plasma Pl 3
SA519761Dog9T3plasma Pl 3
SA519762Dog26T3plasma Pl 3
SA519763Dog24T3plasma Pl 3
SA519764Dog33T3plasma Pl 3
SA519765Dog13T3plasma Pl 3
SA519766QC101pool - -
SA519767QC93pool - -
SA519768QC91pool - -
SA519769QC73pool - -
SA519770QC83pool - -
SA519771QC81pool - -
SA519772QC111pool - -
SA519773QC71pool - -
SA519774QC103pool - -
SA519775QC52pool - -
SA519776QC12pool - -
SA519777QC22pool - -
SA519778QC32pool - -
SA519779QC42pool - -
SA519780QC62pool - -
SA519781QC72pool - -
SA519782QC82pool - -
SA519783QC92pool - -
SA519784QC102pool - -
SA519785QC112pool - -
SA519786QC61pool - -
SA519787QC63pool - -
SA519788QC23pool - -
SA519789QC53pool - -
SA519790QC04pool - -
SA519791QC51pool - -
SA519792QC01pool - -
SA519793QC02pool - -
SA519794QC03pool - -
SA519795QC11pool - -
SA519796QC13pool - -
SA519797QC21pool - -
SA519798QC31pool - -
SA519799QC33pool - -
SA519800QC41pool - -
SA519801QC43pool - -
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Collection:

Collection ID:CO004521
Collection Summary:Pre-prandial plasma samples were collected at T0 and T3, after an 8-hour fast, centrifuged, aliquoted and flash frozen using liquid nitrogen, prior to storage at -80°C until metabolome analysis. 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:Blood (plasma)
Collection Method:Blood collection by veterinarian
Collection Location:Small Animal Department - Ghent University - Merelbeke
Collection Frequency:twice per dog (T0 and T3)
Storage Conditions:-80℃
Collection Vials:Heparine
Storage Vials:Cryotubes

Treatment:

Treatment ID:TR004537
Treatment Summary:Medium chain triglyceride diet OR isocaloric placebo diet (containing long chain triglycerides)

Sample Preparation:

Sampleprep ID:SP004534
Sampleprep Summary:To extract the polar plasma metabolome, 150 µl of plasma was mixed with 600 µl of methanol/acetonitril/aceton (1:1:1) solvens, after the addition of 10 µL ISTD mixture (20 ng/µl of tyrosine-d2, phenylalanine-d2, deoxycholic acid-d4, l-alanine-d3 and dopamine-d4). Subsequent to 2 min of thorough vortexing, proteins were precipitated for 30 min at 4°C.The supernatant of the liquid-liquid extraction was collected after a 10-min centrifugation step (15 000 x g, at 4 %C). Next, the extract was evaporated to dryness using a N-evaporator. The residue was diluted in 200 µl of ultrapure water, vortexed for 30 sec and centrifugated(10 min, 15 000 x g, at 4°C), before transferring to a glass HPLCvial with insert.
Processing Storage Conditions:Described in summary
Extraction Method:liquid-liquid
Extract Storage:4℃
Sample Resuspension:ultrapure water
Sample Spiking:ISTD

Combined analysis:

Analysis ID AN007298 AN007299
Chromatography ID CH005541 CH005541
MS ID MS006992 MS006993
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:CH005541
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:MS006992
Analysis ID:AN007298
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:MS006993
Analysis ID:AN007299
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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