Summary of Study ST003701

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 PR002297. The data can be accessed directly via it's Project DOI: 10.21228/M8QG07 This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study IDST003701
Study TitleTargeted metabolomics investigating the role of aconitate decarboxylase 1 during colitis
Study SummaryWe performed targeted metabolomics on flash frozen colon pieces from naive, Citrobacter rodentium-infected, and DSS-treated WT and Acod1 deficient animals.
Institute
Vanderbilt University
Last NameMcNamara
First NameKara
Address2215 Garland Ave, Nashville, TN 37232
Emailkara.mcnamara@vanderbilt.edu
Phone5087333664
Submit Date2025-01-17
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2026-01-02
Release Version1
Kara McNamara Kara McNamara
https://dx.doi.org/10.21228/M8QG07
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002297
Project DOI:doi: 10.21228/M8QG07
Project Title:Aconitate decarboxylase 1 mediates inflammation in colitis and maintains homeostasis of the metabolome and microbiome
Project Summary:Background & Aims: Aconitate decarboxylase 1 (ACOD1) is implicated in innate immunity and inflammatory responses. We determined the role of ACOD1 in colon inflammation and colitis-associated carcinoma (CAC). Methods: Human inflammatory bowel disease transcriptomic datasets and banked RNA samples were interrogated. C57BL/6 wild-type (WT) and Acod1–/– mice were infected with Citrobacter rodentium or given one or two cycles of 4% dextran sulfate sodium (DSS) as models of colitis. For CAC, mice were given 12.5 mg/kg azoxymethane (AOM) followed by 3 cycles of 4% DSS. Clinical and histological parameters were assessed. Tissues and stool were used for metabolomic and 16S microbiome analyses, respectively. Results: ACOD1 expression is increased in ulcerative colitis (UC) and Crohn’s disease (CD) tissues compared to controls. C. rodentium infection caused body weight loss only in Acod1–/– mice, which had increased histologic injury versus wild-type. In DSS colitis, we observed decreased colon length and increased histologic injury in Acod1–/– versus wild-type mice. There was an altered metabolome in Acod1–/– versus wild-type colon tissues, and during colitis, purine metabolism was most markedly affected. AOM-DSS-treated Acod1–/– animals exhibited more inflammation and injury but no difference in tumorigenesis. 16S microbiome analysis revealed significant differences in phyla and genera; notably an increase in Bacteroidetes and decrease in Proteobacteria in Acod1–/– mice, indicating a dysbiotic state. Conclusions: While ACOD1 is increased in human inflammatory bowel disease (IBD) tissues, our data indicate that this enzyme has a protective role in acute and chronic experimental colitis and is associated with prevention of intestinal dysbiosis and stabilization of the metabolome.
Institute:Vanderbilt University
Last Name:McNamara
First Name:Kara
Address:2215 Garland Ave, Nashville, TN 37232
Email:kara.mcnamara@vanderbilt.edu
Phone:5087333664

Subject:

Subject ID:SU003833
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL/7 WT and Acod1-/- ; Citrobacter rodentium DBS100
Age Or Age Range:8-12 weeks
Gender:Male and female
Animal Animal Supplier:C57BL/6 Acod1–/– mice28 were provided by Dr. Edward Sherwood at Vanderbilt University Medical Center
Animal Housing:VA animal facility
Animal Light Cycle:12 on/ 12 off
Animal Feed:5L0D chow (LabDiet)
Animal Water:Regular water or water with 4% Dextran sulfate sodium (DSS) (TdB Labs)

Factors:

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

mb_sample_id local_sample_id Genotype Treatment
SA405271NEG_S17Acod1 Citrobacter rodentium
SA405272NEG_S19Acod1 Citrobacter rodentium
SA405273NEG_S20Acod1 Citrobacter rodentium
SA405274POS_S20Acod1 Citrobacter rodentium
SA405275POS_S19Acod1 Citrobacter rodentium
SA405276POS_S18Acod1 Citrobacter rodentium
SA405277POS_S17Acod1 Citrobacter rodentium
SA405278POS_S16Acod1 Citrobacter rodentium
SA405279NEG_S16Acod1 Citrobacter rodentium
SA405280NEG_S18Acod1 Citrobacter rodentium
SA405281NEG_S07Acod1 Control
SA405282NEG_S06Acod1 Control
SA405283POS_S10Acod1 Control
SA405284POS_S09Acod1 Control
SA405285POS_S08Acod1 Control
SA405286POS_S07Acod1 Control
SA405287POS_S06Acod1 Control
SA405288NEG_S08Acod1 Control
SA405289NEG_S09Acod1 Control
SA405290NEG_S10Acod1 Control
SA405291POS_S27Acod1 Dextran sulfate sodium
SA405292POS_S30Acod1 Dextran sulfate sodium
SA405293POS_S29Acod1 Dextran sulfate sodium
SA405294POS_S28Acod1 Dextran sulfate sodium
SA405295NEG_S27Acod1 Dextran sulfate sodium
SA405296POS_S26Acod1 Dextran sulfate sodium
SA405297NEG_S26Acod1 Dextran sulfate sodium
SA405298NEG_S28Acod1 Dextran sulfate sodium
SA405299NEG_S29Acod1 Dextran sulfate sodium
SA405300NEG_S30Acod1 Dextran sulfate sodium
SA405301NEG_S12WT Citrobacter rodentium
SA405302POS_S15WT Citrobacter rodentium
SA405303POS_S14WT Citrobacter rodentium
SA405304POS_S13WT Citrobacter rodentium
SA405305NEG_S15WT Citrobacter rodentium
SA405306NEG_S14WT Citrobacter rodentium
SA405307NEG_S13WT Citrobacter rodentium
SA405308POS_S12WT Citrobacter rodentium
SA405309POS_S11WT Citrobacter rodentium
SA405310NEG_S11WT Citrobacter rodentium
SA405311POS_S01WT Control
SA405312NEG_S05WT Control
SA405313NEG_S04WT Control
SA405314POS_S03WT Control
SA405315POS_S04WT Control
SA405316POS_S05WT Control
SA405317NEG_S01WT Control
SA405318NEG_S02WT Control
SA405319POS_S02WT Control
SA405320NEG_S03WT Control
SA405321POS_S24WT Dextran sulfate sodium
SA405322POS_S23WT Dextran sulfate sodium
SA405323NEG_S21WT Dextran sulfate sodium
SA405324POS_S25WT Dextran sulfate sodium
SA405325NEG_S23WT Dextran sulfate sodium
SA405326NEG_S24WT Dextran sulfate sodium
SA405327NEG_S25WT Dextran sulfate sodium
SA405328POS_S22WT Dextran sulfate sodium
SA405329POS_S21WT Dextran sulfate sodium
SA405330NEG_S22WT Dextran sulfate sodium
Showing results 1 to 60 of 60

Collection:

Collection ID:CO003826
Collection Summary:Flash frozen colonic tissues from C. rodentium-infected or DSS-treated WT and Acod1–/– animals were subjected to untargeted metabolomic analysis.
Sample Type:Colon
Storage Conditions:Described in summary

Treatment:

Treatment ID:TR003842
Treatment Summary:Mice were inoculated with a single sublethal dose of 5 x 108 C. rodentium DBS100 via oral gavage. Control mice received sterile Luria-Bertani broth. Animals were monitored and weighed daily for 14 days. At day 14, mice were sacrificed, and the colons were removed, measured, cleaned, and weighed. Proximal and distal pieces of colon were collectedand flash frozen for metabolomic analysis. In the acute model of DSS-induced colitis, WT and Acod1–/– mice were treated with 4% DSS (TdB Labs) in their drinking water for 5 days before the DSS was removed and replaced with regular water for an additional 5 days. At day 10, mice were sacrificed, and the colons were removed, measured, cleaned, and weighed. Proximal and distal pieces of colon were collectedand flash frozen for metabolomic analysis.
Treatment Dose:5 x 108 C. rodentium and 4% DSS
Treatment Doseduration:14 days for bacteria and 5 days of DSS
Animal Endp Euthanasia:14 days and 10 days

Sample Preparation:

Sampleprep ID:SP003840
Sampleprep Summary:Lipid extraction and tandem mass spectrometry: To evaluate differences in hepatic lipid metabolism tandem mass spectrometry of extracted lipids was performed. For this purpose, 10 mg liver tissue was homogenized in 500 μL ddH2O on ice. Then, 50 μL of the homogenate was transferred into a fresh Eppendorf tube and 500 μL Extraction Mix (CHCl3/MeOH 1/5 containing the following internal standards: 210 pmol PE(31:1), 396 pmol PC(31:1), 98 pmol PS(31:1), 84 pmol PI(34:0), 56 pmol PA(31:1), 51 pmol PG (28:0), 28 pmol CL(56:0), 39 pmol LPA (17:0), 35 pmol LPC(17:1), 38 pmol LPE (17:0), 32 pmol Cer(17:0), 99 pmol, SM(17:0), 55 pmol GlcCer(12:0), 14 pmol GM3 (18:0-D3), 339 pmol TG(50:1-d4), 111 pmol, CE(17:1), 64 pmol DG(31:1), 103 pmol MG(17:1), 724 pmol Chol(d6) and 45 pmol Car(15:0) was added. After 2 min of sonication in a bath sonicator, the samples were spun at 20,000 g for 2 min. The supernatant was collected in a new Eppendorf tube and 200 μL chloroform and 750 μL of 1 M Ammonium acetate (NH4Ac) in ddH2O were added. Following quick manual shaking, the samples were centrifuged at 20,000 g for 2 min again. The upper phase was carefully removed, and the lower phase was transferred into a new Eppendorf tube. The solvent was evaporated using a SpeedVac Vacuum Concentrator at 45 °C for 20 min. The dried lipids were dissolved in 500 μL Spray Buffer (Isopropanol, Methanol, ddH2O (all MS grade), 10 mM ammonium acetate, 0.1 % acetic acid by sonication for 5 min. Until measurement with a Thermo Q Exactive ™ Plus (Thermo Scientific) using positive mode, the samples were stored at -20 °C. Before the acquisition, the samples were sonicated for 5 min.

Combined analysis:

Analysis ID AN006072 AN006073
Chromatography ID CH004612 CH004612
MS ID MS005779 MS005780
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Waters Acquity Waters Acquity
Column Merck Zic-cHILIC analytical (150 x 2.1mm, 3um) Merck Zic-cHILIC analytical (150 x 2.1mm, 3um)
MS Type ESI ESI
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name Thermo TSQ Quantum Ultra Thermo TSQ Quantum Ultra
Ion Mode POSITIVE NEGATIVE
Units Normalized peak area Normalized peak area

Chromatography:

Chromatography ID:CH004612
Chromatography Summary:HILIC-LC. Solvent A: 0.2 % acetic acid and 15 mM ammonium acetate in H2O/CH3CN (9:1); Solvent B: 0.2 % acetic acid and 15 mM ammonium acetate in CH3CN/CH3OH/H2O (90:5:5)
Instrument Name:Waters Acquity
Column Name:Merck Zic-cHILIC analytical (150 x 2.1mm, 3um)
Column Temperature:22
Flow Gradient:0min, 85% B; 2min, 85% B; 5min, 30% B; 9min, 30% B; 11min, 85% B; 20min, 85% B
Flow Rate:0.3mL/min
Solvent A:90% water/10% acetonitrile; 0.2% acetic acid; 15mM ammonium acetate
Solvent B:90% acetonitrile/5% methanol/5% water; 0.2% acetic acid; 15mM ammonium acetate
Chromatography Type:HILIC

MS:

MS ID:MS005779
Analysis ID:AN006072
Instrument Name:Thermo TSQ Quantum Ultra
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:MS acquisition: 20 min; Data processing: Thermo LCQuan
Ion Mode:POSITIVE
  
MS ID:MS005780
Analysis ID:AN006073
Instrument Name:Thermo TSQ Quantum Ultra
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:MS acquisition: 20 min; Data processing: Thermo LCQuan
Ion Mode:NEGATIVE
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