Summary of Study ST001075
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 PR000720. The data can be accessed directly via it's Project DOI: 10.21228/M8M977 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 | ST001075 |
| Study Title | Integrated metabolome and transcriptome analyses provide novel insight into colon cancer modulation by the gut microbiota |
| Study Summary | Colon cancer onset and progression is strongly associated with the presence, absence, or relative abundances of certain microbial taxa in the gastrointestinal tract. However, specific mechanisms affecting disease susceptibility related to complex commensal bacterial mixtures are poorly understood. We used a multi-omics approach to determine how differences in the complex gut microbiome (GM) influence the metabolome and host transcriptome and ultimately affect susceptibility to adenoma development. Fecal samples collected from a preclinical rat model of colon cancer harboring distinct complex GMs were analyzed using ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS). We collected samples prior to observable disease onset and identified putative metabolite profiles that predicted future disease severity, independent of GM status. Transcriptome analyses performed after disease onset from normal epithelium and tumor tissues between the high and low tumor GMs suggests that the GM is also correlated with altered host gene expression. Integrated pathway (IP) analyses of the metabolome and transcriptome based on putatively identified metabolic features indicate that bile acid biosynthesis was enriched in rats with high tumors (GM:F344) along with increased fatty acid metabolism and mucin biosynthesis. These data emphasize the utility of using untargeted metabolomics to reveal signatures of susceptibility and resistance and integrated analysis reveals common pathways that are likely to be universal targets for intervention. |
| Institute | University of Missouri-Columbia |
| Last Name | Busi |
| First Name | Susheel Bhanu |
| Address | 4011 Discovery Drive N121 |
| SB6F4@MAIL.MISSOURI.EDU | |
| Phone | 2404094390 |
| Submit Date | 2018-10-10 |
| Num Groups | 3 |
| Total Subjects | 13 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | cdf |
| Analysis Type Detail | GC-MS |
| Release Date | 2019-01-22 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR000720 |
| Project DOI: | doi: 10.21228/M8M977 |
| Project Title: | Integrated metabolome and transcriptome analyses provide novel insight into colon cancer modulation by the gut microbiota |
| Project Summary: | Colon cancer onset and progression is strongly associated with the presence, absence, or relative abundances of certain microbial taxa in the gastrointestinal tract. However, specific mechanisms affecting disease susceptibility related to complex commensal bacterial mixtures are poorly understood. We used a multi-omics approach to determine how differences in the complex gut microbiome (GM) influence the metabolome and host transcriptome and ultimately affect susceptibility to adenoma development. Fecal samples collected from a preclinical rat model of colon cancer harboring distinct complex GMs were analyzed using ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS). We collected samples prior to observable disease onset and identified putative metabolite profiles that predicted future disease severity, independent of GM status. Transcriptome analyses performed after disease onset from normal epithelium and tumor tissues between the high and low tumor GMs suggests that the GM is also correlated with altered host gene expression. Integrated pathway (IP) analyses of the metabolome and transcriptome based on putatively identified metabolic features indicate that bile acid biosynthesis was enriched in rats with high tumors (GM:F344) along with increased fatty acid metabolism and mucin biosynthesis. These data emphasize the utility of using untargeted metabolomics to reveal signatures of susceptibility and resistance and integrated analysis reveals common pathways that are likely to be universal targets for intervention. |
| Institute: | University of Missouri |
| Department: | Veterinary Pathobiology |
| Laboratory: | Amos-Landgraf |
| Last Name: | Busi |
| First Name: | Susheel Bhanu |
| Address: | 4011 Discovery Drive, N121 |
| Email: | sb6f4@mail.missouri.edu |
| Phone: | 2404094390 |
| Contributors: | Zhentian Lei, James Amos-Landgraf, Lloyd W. Sumner, |
Subject:
| Subject ID: | SU001119 |
| Subject Type: | Mammal |
| Subject Species: | Rattus norvegicus |
| Taxonomy ID: | 10116 |
| Genotype Strain: | F344/Ntac-Apc-+/Pirc |
| Age Or Age Range: | 30 |
| Animal Animal Supplier: | Taconic and Envigo |
| Animal Housing: | Conventional, |
| Animal Feed: | Labdiet 5058 |
| Animal Water: | Autoclaved, purified with sulfuric acid |
Factors:
Subject type: Mammal; Subject species: Rattus norvegicus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Group |
|---|---|---|
| SA072510 | SB4 | GM;F344 |
| SA072511 | SB3 | GM;F344 |
| SA072512 | SB1 | GM;F344 |
| SA072513 | SB2 | GM;F344 |
| SA072514 | SB8 | GM;LEW |
| SA072515 | SB7 | GM;LEW |
| SA072516 | SB6 | GM;LEW |
| SA072517 | SB5 | GM;LEW |
| SA072518 | SB12 | GM;SD |
| SA072519 | SB13 | GM;SD |
| SA072520 | SB11 | GM;SD |
| SA072521 | SB9 | GM;SD |
| SA072522 | SB10 | GM;SD |
| Showing results 1 to 13 of 13 |
Collection:
| Collection ID: | CO001113 |
| Collection Summary: | Fecal samples collected at 1 month of age, prior to any observable disease onset. F344 refers to Fisher (F344) rats, whereas as GM:SD refers to the GM from Sprague-Dawley rats, while GM:LEW refers to the gut microbiota (GM) from Lewis rats |
| Collection Protocol ID: | 8732 |
| Sample Type: | Feces |
| Collection Method: | Sterile, asceptic method. Animals were placed in clean, sterile cages and feces were speared with sterile, autoclaved toothpicks. |
| Collection Location: | Discovery Ridge, Columbia MO |
| Storage Conditions: | -80℃ |
| Collection Vials: | Glass |
| Storage Vials: | Glass |
Treatment:
| Treatment ID: | TR001133 |
| Treatment Summary: | Pirc rats were rederived using 3 surrogate dams, each with distinct gut microbiota profiles |
| Treatment Protocol ID: | 8732 |
Sample Preparation:
| Sampleprep ID: | SP001126 |
| Sampleprep Summary: | Fecal samples were lyophilized at -20 ˚C using 0.1 millibar of vacuum pressure, following which dried samples (30 mg) were extracted sequentially for both UHPLC-MS and GC-MS. The dried samples were first treated with 1.0 mL of 80% MeOH containing 18 µg/mL umbelliferone, sonicated for 5 minutes and centrifuged for 40 minutes at 3000 g at 10 ºC. 0.5 mL of supernatant was used for UHPLC-MS analysis after a subsequent spin at 5000 g at 10 ºC for 20 minutes and transferring 250 µL of the sample into glass autosampler vials with inserts. For GC-MS (Gas Chromatography-Mass Spectrometry) analyses of primary polar metabolites, 0.5 mL water was added the remaining extract used above for the UHPLC preparation, sonicated for 5 min, extracted for 30min, and centrifuged at 3000 g. 0.5 mL of the polar extract was subsequently dried under nitrogen and derivatized using previously established protocols (84). Briefly, N-Methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA) with 1 % TMCS (2,2,2-Trifluoro-N-methyl-N-(trimethylsilyl)-acetamide, Chlorotrimethylsilane) was used to derivatize the polar metabolites, after treatment with methoxyamine-HCl-pyridine. |
Combined analysis:
| Analysis ID | AN001757 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Agilent 1290 |
| Column | Waters Acquity BEH C18 (150 x 2.1mm,1.7um) |
| MS Type | ESI |
| MS instrument type | QTOF |
| MS instrument name | Bruker maXis Impact qTOF |
| Ion Mode | NEGATIVE |
| Units | Peak Area |
Chromatography:
| Chromatography ID: | CH001241 |
| Instrument Name: | Agilent 1290 |
| Column Name: | Waters Acquity BEH C18 (150 x 2.1mm,1.7um) |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS001625 |
| Analysis ID: | AN001757 |
| Instrument Name: | Bruker maXis Impact qTOF |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| Ion Mode: | NEGATIVE |
