Summary of Study ST003909
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 PR002446. The data can be accessed directly via it's Project DOI: 10.21228/M8G834 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003909 |
| Study Title | Colesevelam induced serum and fecal metabolite profile in Mdr2 WT and KO mice - Serum |
| Study Summary | Multidrug resistance protein 2 (MDR2) is essential for proper bile acid transport, and its deficiency leads to spontaneous development of chronic cholestatic liver disease resembling primary sclerosing cholangitis (PSC). To investigate the metabolic consequences of MDR2 loss and the therapeutic effects of bile acid sequestration, we utilized an Mdr2-knockout mouse model and performed fecal and serum metabolomic profiling. Comparative analyses between Mdr2 wildtype and knockout mice revealed significant alterations in bile acid–related metabolites and inflammatory metabolic signatures. Upon treatment with colesevelam, a clinically approved bile acid sequestrant, we observed a marked attenuation of hepatic inflammation and fibrosis. Metabolomic shifts following colesevelam administration highlighted specific metabolite changes potentially responsible for the observed hepatic improvement. These findings suggest a mechanistic link between bile acid modulation, systemic metabolism, and hepatic pathology, offering insights into the therapeutic potential of metabolic intervention in PSC. Serum metabolite showes significant change in bile acid metabolism associated metabolites by treatment of colesevelam |
| Institute | Kyung Hee University |
| Last Name | June-Young |
| First Name | Lee |
| Address | Kyungheedae-ro 26, Seoul, South Korea |
| hgod2356@khu.ac.kr | |
| Phone | +8210-7720-0118 |
| Submit Date | 2025-05-01 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-05-14 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002446 |
| Project DOI: | doi: 10.21228/M8G834 |
| Project Title: | Fecal and serum untargeted metabolomics analysis in MDR2 WT, KO mouse |
| Project Summary: | Colesevelam treatment induces significant change of serum and fecal metabolite profile in Primary sclerosing cholangitis mouse model We aimed to identify metabolites differing between Mdr2 WT and KO mice through fecal and serum metabolomic analyses, and to determine whether changes in specific metabolites induced by the bile acid sequestrant colesevelam contribute to the amelioration of liver pathology. |
| Institute: | Kyung Hee University |
| Last Name: | June-Young |
| First Name: | Lee |
| Address: | Kyungheedae-ro 26, Seoul, South Korea |
| Email: | hgod2356@khu.ac.kr |
| Phone: | +8210-7720-0118 |
Subject:
| Subject ID: | SU004044 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | FVB.129P2-Abcb4tm1Bor/J |
| Gender: | Male |
| Animal Animal Supplier: | Jackson |
| Animal Housing: | Kyung Hee University |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype | Treatment |
|---|---|---|---|
| SA430082 | KO-COL11_Serum_positive | Mdr2-knockout | Colesevelam |
| SA430083 | KO-COL9_Serum_negative | Mdr2-knockout | Colesevelam |
| SA430084 | KO-COL8_Serum_negative | Mdr2-knockout | Colesevelam |
| SA430085 | KO-COL7_Serum_negative | Mdr2-knockout | Colesevelam |
| SA430086 | KO-COL6_Serum_negative | Mdr2-knockout | Colesevelam |
| SA430087 | KO-COL5_Serum_negative | Mdr2-knockout | Colesevelam |
| SA430088 | KO-COL15_Serum_negative | Mdr2-knockout | Colesevelam |
| SA430089 | KO-COL11_Serum_negative | Mdr2-knockout | Colesevelam |
| SA430090 | KO-COL10_Serum_positive | Mdr2-knockout | Colesevelam |
| SA430091 | KO-COL10_Serum_negative | Mdr2-knockout | Colesevelam |
| SA430092 | KO-COL9_Serum_positive | Mdr2-knockout | Colesevelam |
| SA430093 | KO-COL15_Serum_positive | Mdr2-knockout | Colesevelam |
| SA430094 | KO-COL5_Serum_positive | Mdr2-knockout | Colesevelam |
| SA430095 | KO-COL7_Serum_positive | Mdr2-knockout | Colesevelam |
| SA430096 | KO-COL8_Serum_positive | Mdr2-knockout | Colesevelam |
| SA430097 | KO-COL6_Serum_positive | Mdr2-knockout | Colesevelam |
| SA430098 | KO-VEH14_Serum_positive | Mdr2-knockout | Vehicle |
| SA430099 | KO-VEH10_Serum_positive | Mdr2-knockout | Vehicle |
| SA430100 | KO-VEH9_Serum_negative | Mdr2-knockout | Vehicle |
| SA430101 | KO-VEH5_Serum_negative | Mdr2-knockout | Vehicle |
| SA430102 | KO-VEH4_Serum_negative | Mdr2-knockout | Vehicle |
| SA430103 | KO-VEH3_Serum_negative | Mdr2-knockout | Vehicle |
| SA430104 | KO-VEH14_Serum_negative | Mdr2-knockout | Vehicle |
| SA430105 | KO-VEH10_Serum_negative | Mdr2-knockout | Vehicle |
| SA430106 | KO-VEH4_Serum_positive | Mdr2-knockout | Vehicle |
| SA430107 | KO-VEH5_Serum_positive | Mdr2-knockout | Vehicle |
| SA430108 | KO-VEH3_Serum_positive | Mdr2-knockout | Vehicle |
| SA430109 | KO-VEH9_Serum_positive | Mdr2-knockout | Vehicle |
| SA430110 | KO-VEH11_Serum_negative | Mdr2-knockout | Vehicle |
| SA430111 | KO-VEH11_Serum_positive | Mdr2-knockout | Vehicle |
| SA430112 | WT-COL6_Serum_positive | Wild-type | Colesevelam |
| SA430113 | WT-COL8_Serum_negative | Wild-type | Colesevelam |
| SA430114 | WT-COL6_Serum_negative | Wild-type | Colesevelam |
| SA430115 | WT-COL3_Serum_negative | Wild-type | Colesevelam |
| SA430116 | WT-COL2_Serum_negative | Wild-type | Colesevelam |
| SA430117 | WT-COL1_Serum_negative | Wild-type | Colesevelam |
| SA430118 | WT-COL12_Serum_negative | Wild-type | Colesevelam |
| SA430119 | WT-COL12_Serum_positive | Wild-type | Colesevelam |
| SA430120 | WT-COL3_Serum_positive | Wild-type | Colesevelam |
| SA430121 | WT-COL10_Serum_negative | Wild-type | Colesevelam |
| SA430122 | WT-COL8_Serum_positive | Wild-type | Colesevelam |
| SA430123 | WT-COL2_Serum_positive | Wild-type | Colesevelam |
| SA430124 | WT-COL10_Serum_positive | Wild-type | Colesevelam |
| SA430125 | WT-COL1_Serum_positive | Wild-type | Colesevelam |
| SA430126 | WT-VEH14_Serum_positive | Wild-type | Vehicle |
| SA430127 | WT-VEH1_Serum_positive | Wild-type | Vehicle |
| SA430128 | WT-VEH2_Serum_positive | Wild-type | Vehicle |
| SA430129 | WT-VEH4_Serum_positive | Wild-type | Vehicle |
| SA430130 | WT-VEH7_Serum_positive | Wild-type | Vehicle |
| SA430131 | WT-VEH8_Serum_positive | Wild-type | Vehicle |
| SA430132 | WT-VEH11_Serum_positive | Wild-type | Vehicle |
| SA430133 | WT-VEH11_Serum_negative | Wild-type | Vehicle |
| SA430134 | WT-VEH14_Serum_negative | Wild-type | Vehicle |
| SA430135 | WT-VEH1_Serum_negative | Wild-type | Vehicle |
| SA430136 | WT-VEH2_Serum_negative | Wild-type | Vehicle |
| SA430137 | WT-VEH4_Serum_negative | Wild-type | Vehicle |
| SA430138 | WT-VEH7_Serum_negative | Wild-type | Vehicle |
| SA430139 | WT-VEH8_Serum_negative | Wild-type | Vehicle |
| Showing results 1 to 58 of 58 |
Collection:
| Collection ID: | CO004037 |
| Collection Summary: | Fecal and serum samples were collected from Mdr2-knockout and wildtype mice following an 8-week treatment period with either colesevelam or vehicle control. Fecal samples were directly collected at the end of the treatment period, while serum samples were obtained via cardiac puncture immediately prior to liver tissue harvest. For metabolomic analysis, 0.04 g of fecal material and 100 μL of serum were used per sample. All samples were snap-frozen and stored at –80 °C until extraction. No in vitro cell lines were used in this study. |
| Sample Type: | Blood (serum) |
| Collection Location: | Serum |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR004053 |
| Treatment Summary: | FVB/N wild-type (WT, Mdr2+/+) and Mdr2−/− (knock-out, KO) littermate mice were obtained by breeding heterozygous pairs bought from the Jackson Laboratory (Bar Habor, Maine, USA). WT and KO littermates were housed under a 12-hour light/dark cycle, and allowed access to water and a standard chow diet (2918C; Envigo) ad libitum. Both WT and KO mice were randomly assigned to cages for each group (vehicle- and colesevelam-treated) at 3–4 weeks of age. Colesevelam (a BA sequestrant, cas#182815-44-7) was obtained from BOC Sciences (Ramsey Road Shirley, NY, USA). From 7–8 weeks of age, male Mdr2+/+ and Mdr2−/− littermate mice received either a control chow diet or a diet supplemented with 2% (w/w) colesevelam for 8 weeks. |
| Treatment Compound: | normal chow diet or Colesevelam included diet |
| Treatment Route: | oral route |
| Treatment Dose: | 2% (w/w) colesevelam |
| Treatment Doseduration: | 8 weeks |
| Treatment Vehicle: | normal chow diet |
Sample Preparation:
| Sampleprep ID: | SP004050 |
| Sampleprep Summary: | Serum and fecal samples were thawed at 4°C before extraction. Briefly, 100 μL of serum and 0.04 g of feces was added to 900 μL of a solution comprising MeOH:acetonitrile:water (1:1:2, v/v) containing reserpine 10 μM and 0.1% (v/v) formic acid. The serum and fecal solutions were then homogenized by vortexing for 5 min, followed by centrifugation at 13,000 × g at 4°C for 10 min. After centrifugation, the supernatant was filtered through a 0.2 μm pore polytetrafluoroethylene polymer filter and transferred to a new glass vial. Quality control (QC) samples were prepared by mixing 50 μL of filtered samples (serum and feces). QC samples were analyzed together and inserted into every five samples regularly before and after the operation. |
| Sampleprep Protocol Filename: | JYL_protocol.pdf |
| Extract Storage: | On ice |
Chromatography:
| Chromatography ID: | CH004866 |
| Chromatography Summary: | see protocol file |
| Methods Filename: | JYL_protocol.pdf |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Agilent ZORBAX Eclipse Plus C18 (100 x 2.1mm,3.5um) |
| Column Temperature: | 45 |
| Flow Gradient: | The gradient started with 98% A, decreasing to 10% A in 13 min, holding at 10% A for 3 min, moving immediately to 98% A, and then holding at 98% A for 4 min. |
| Flow Rate: | 0.5 mL/min |
| Solvent A: | 100% water; 0.1% formic acid |
| Solvent B: | 100% acetonitrile; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN006416 |
| Laboratory Name: | Seoul Biohub |
| Analysis Type: | MS |
| Analysis Protocol File: | JYL_protocol.pdf |
| Acquisition Date: | 2023.08 |
| Software Version: | Xcalibur, version 4.1.31.9 |
| Data Format: | RAW |
| Chromatography ID: | CH004866 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Seconds |
| Results File: | ST003909_AN006416_Results.txt |
| Units: | peak area |
| Analysis ID: | AN006417 |
| Laboratory Name: | Seoul Biohub |
| Analysis Type: | MS |
| Analysis Protocol File: | JYL_protocol.pdf |
| Acquisition Date: | 2023.08 |
| Software Version: | Xcalibur, version 4.1.31.9 |
| Data Format: | RAW |
| Chromatography ID: | CH004866 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Seconds |
| Results File: | ST003909_AN006417_Results.txt |
| Units: | peak area |
