Summary of Study ST003700
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
| Study ID | ST003700 |
| Study Title | Untargeted metabolomics investigating the role of aconitate decarboxylase 1 during colitis |
| Study Summary | We performed untargeted metabolomics on flash frozen colonic tissue from naive, Citrobacter rodentium-infected, and DSS-treated WT and Acod1 deficient mice. |
| Institute | Vanderbilt University |
| Last Name | McNamara |
| First Name | Kara |
| Address | 2215 Garland Ave, Nashville, TN 37232 |
| kara.mcnamara@vanderbilt.edu | |
| Phone | 5087333664 |
| Submit Date | 2025-01-17 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2026-01-02 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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: | SU003832 |
| 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 |
|---|---|---|---|
| SA405241 | S17 | Acod1 | Citrobacter rodentium |
| SA405242 | S20 | Acod1 | Citrobacter rodentium |
| SA405243 | S19 | Acod1 | Citrobacter rodentium |
| SA405244 | S18 | Acod1 | Citrobacter rodentium |
| SA405245 | S16 | Acod1 | Citrobacter rodentium |
| SA405246 | S07 | Acod1 | Control |
| SA405247 | S09 | Acod1 | Control |
| SA405248 | S10 | Acod1 | Control |
| SA405249 | S06 | Acod1 | Control |
| SA405250 | S08 | Acod1 | Control |
| SA405251 | S26 | Acod1 | Dextran sulfate sodium |
| SA405252 | S30 | Acod1 | Dextran sulfate sodium |
| SA405253 | S29 | Acod1 | Dextran sulfate sodium |
| SA405254 | S28 | Acod1 | Dextran sulfate sodium |
| SA405255 | S27 | Acod1 | Dextran sulfate sodium |
| SA405256 | S11 | WT | Citrobacter rodentium |
| SA405257 | S12 | WT | Citrobacter rodentium |
| SA405258 | S13 | WT | Citrobacter rodentium |
| SA405259 | S14 | WT | Citrobacter rodentium |
| SA405260 | S15 | WT | Citrobacter rodentium |
| SA405261 | S04 | WT | Control |
| SA405262 | S05 | WT | Control |
| SA405263 | S03 | WT | Control |
| SA405264 | S02 | WT | Control |
| SA405265 | S01 | WT | Control |
| SA405266 | S23 | WT | Dextran sulfate sodium |
| SA405267 | S24 | WT | Dextran sulfate sodium |
| SA405268 | S25 | WT | Dextran sulfate sodium |
| SA405269 | S22 | WT | Dextran sulfate sodium |
| SA405270 | S21 | WT | Dextran sulfate sodium |
| Showing results 1 to 30 of 30 |
Collection:
| Collection ID: | CO003825 |
| Collection Summary: | Flash frozen colonic tissues from C. rodentium-infected or DSS-treated WT and Acod1–/– animals were subjected to untargeted metabolomic analysis. |
| Collection Protocol Filename: | Metabolomics Protocol |
| Sample Type: | Colon |
| Storage Conditions: | Described in summary |
Treatment:
| Treatment ID: | TR003841 |
| 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: | Either infection with Citrobacter rodentium for 14 days or treated with 4% DSS in their drinking water for 5 days |
| Treatment Route: | Oral gavage for the bacteria and in the drinking water for the DSS |
| 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: | SP003839 |
| Sampleprep Summary: | Flash frozen pieces of colon were used for the untargeted metabolomics. Colonic tissues were homogenized by sonication in water:methanol (9:1) containing 50 mM ammonium acetate (pH ~6) to yield a tissue density of 50 mg/ml. An aliquot of the homogenate was combined with HPLC-grade methanol, vortexed vigorously, and centrifuged. The supernatant was diluted with an equal volume of HPLC- grade acetonitrile. |
| Processing Storage Conditions: | Described in summary |
| Extract Storage: | Described in summary |
Combined analysis:
| Analysis ID | AN006070 | AN006071 |
|---|---|---|
| Chromatography ID | CH004611 | CH004611 |
| MS ID | MS005777 | MS005778 |
| Analysis type | MS | MS |
| Chromatography type | HILIC | HILIC |
| Chromatography system | Thermo Vanquish UHPLC | Thermo Vanquish UHPLC |
| Column | Agilent InfinityLab Poroshell 120 HILIC-Z (150 x 2.1mm, 1.9 um) | Agilent InfinityLab Poroshell 120 HILIC-Z (150 x 2.1mm, 1.9 um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive HF hybrid Orbitrap | Thermo Q Exactive HF hybrid Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Peak area | Peak area |
Chromatography:
| Chromatography ID: | CH004611 |
| Chromatography Summary: | UHPLC HILIC mode |
| Instrument Name: | Thermo Vanquish UHPLC |
| Column Name: | Agilent InfinityLab Poroshell 120 HILIC-Z (150 x 2.1mm, 1.9 um) |
| 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: | 300 uL/min |
| Solvent A: | 90% water/10% acetonitrile; 0.2% acetic acid; 15 mM ammonium acetate |
| Solvent B: | 90% acetonitrile/5% methanol/5% water; 0.2% acetic acid; 15 mM ammonium acetate |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS005777 |
| Analysis ID: | AN006070 |
| Instrument Name: | Thermo Q Exactive HF hybrid Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | data dependent acquisition with 60k resolution for MS1 and 15K resolution for MS2; data was processed with MS-Dial ver 4.90 and further processed using Excel and Metaboanalyst |
| Ion Mode: | POSITIVE |
| MS ID: | MS005778 |
| Analysis ID: | AN006071 |
| Instrument Name: | Thermo Q Exactive HF hybrid Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | data dependent acquisition with 60k resolution for MS1 and 15K resolution for MS2; data was processed with MS-Dial ver 4.90 and further processed using Excel and Metaboanalyst |
| Ion Mode: | NEGATIVE |
