Summary of project PR002297
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
| 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 |
Summary of all studies in project PR002297
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003700 | Untargeted metabolomics investigating the role of aconitate decarboxylase 1 during colitis | Mus musculus | Vanderbilt University | MS* | 2026-01-02 | 1 | 30 | Uploaded data (1.1G)* |
| ST003701 | Targeted metabolomics investigating the role of aconitate decarboxylase 1 during colitis | Mus musculus | Vanderbilt University | MS | 2026-01-02 | 1 | 60 | Uploaded data (96.2M)* |
