Summary of Study ST003054

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 PR001903. The data can be accessed directly via it's Project DOI: 10.21228/M8R14K This work is supported by NIH grant, U2C- DK119886.

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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.

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Study IDST003054
Study TitleIntegrated metabolomics and proteomics of symptomatic and early pre-symptomatic states of colitis
Study SummaryColitis has a multifactorial pathogenesis with a strong cross-talk among microbiota, hypoxia and tissue metabolism. Here, we aimed to characterize the molecular signature of the disease in symptomatic and pre-symptomatic stages of the inflammatory process at the tissue and fecal level. The study is based on two different murine models for colitis. High-resolution Magic Angle Spinning NMR on cryopreserved “intact” colon tissues and LC-MS/MS on colon tissue extracts were used to derive untargeted metabolomics and proteomics information, respectively. Solution NMR was used to derive metabolomic profiles of fecal extracts. By combining metabolomic and proteomic analyses of the tissues, we found increased anaerobic glycolysis, accompanied by altered citric acid cycle and oxidative phosphorylation in inflamed colons; these changes associate with inflammation-induced hypoxia taking place in colon tissues. Pre-symptomatic states can be discriminated from healthy samples before macroscopic inflammation is observed. Different colitis states are characterized by significantly different metabolomic profiles of fecal extracts, attributable to both the dysbiosis characteristic of colitis, as well as the dysregulated tissue metabolism. Strong and distinctive fecal metabolomic signatures can be detected before onset of symptoms. Therefore, untargeted metabolomics of tissues and fecal extracts provides a comprehensive picture of the changes accompanying the disease onset already at pre-clinical stages, highlighting the diagnostic potential of global metabolomics for inflammatory diseases.
Institute
University of Florence
Last NameGhini
First NameVeronica
Addressvia Luigi Sacconi, 6, Sesto Fiorentino, Firenze, 50019, Italy
Emailghini@cerm.unifi.it
Phone+390554574266
Submit Date2024-01-23
Num Groups5
Total Subjects50
Raw Data AvailableYes
Raw Data File Type(s)fid
Analysis Type DetailNMR
Release Date2024-02-28
Release Version1
Veronica Ghini Veronica Ghini
https://dx.doi.org/10.21228/M8R14K
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001903
Project DOI:doi: 10.21228/M8R14K
Project Title:Integrated metabolomics and proteomics of symptomatic and early pre-symptomatic states of colitis
Project Type:NMR-based metabolomics
Project Summary:Colitis has a multifactorial pathogenesis with a strong cross-talk among microbiota, hypoxia and tissue metabolism. Here, we aimed to characterize the molecular signature of the disease in symptomatic and pre-symptomatic stages of the inflammatory process at the tissue and fecal level. The study is based on two different murine models for colitis. High-resolution Magic Angle Spinning NMR on cryopreserved “intact” colon tissues and LC-MS/MS on colon tissue extracts were used to derive untargeted metabolomics and proteomics information, respectively. Solution NMR was used to derive metabolomic profiles of fecal extracts. By combining metabolomic and proteomic analyses of the tissues, we found increased anaerobic glycolysis, accompanied by altered citric acid cycle and oxidative phosphorylation in inflamed colons; these changes associate with inflammation-induced hypoxia taking place in colon tissues. Pre-symptomatic states can be discriminated from healthy samples before macroscopic inflammation is observed. Different colitis states are characterized by significantly different metabolomic profiles of fecal extracts, attributable to both the dysbiosis characteristic of colitis, as well as the dysregulated tissue metabolism. Strong and distinctive fecal metabolomic signatures can be detected before onset of symptoms. Therefore, untargeted metabolomics of tissues and fecal extracts provides a comprehensive picture of the changes accompanying the disease onset already at pre-clinical stages, highlighting the diagnostic potential of global metabolomics for inflammatory diseases.
Institute:University of Florence
Department:Department of Chemistry
Laboratory:Metabolomics
Last Name:Ghini
First Name:Veronica
Address:via Luigi Sacconi, 6, Sesto Fiorentino, Firenze, 50019, Italy
Email:ghini@cerm.unifi.it
Phone:+390554574266

Subject:

Subject ID:SU003169
Subject Type:Mammal
Subject Species:Mus musculus
Gender:Male and female

Factors:

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

mb_sample_id local_sample_id Group
SA331564WT_DSS_4Day_10_DSS
SA331565WT_DSS_3Day_10_DSS
SA331566WT_DSS_1Day_10_DSS
SA331567WT_DSS_5Day_10_DSS
SA331568WT_DSS_10Day_10_DSS
SA331569WT_DSS_2Day_10_DSS
SA331570WT_DSS_6Day_10_DSS
SA331571WT_DSS_9Day_10_DSS
SA331572WT_DSS_8Day_10_DSS
SA331573WT_DSS_7Day_10_DSS
SA331574WT_DSS4_3Day_4_DSS
SA331575WT_DSS4_2Day_4_DSS
SA331576WT_DSS4_10Day_4_DSS
SA331577WT_DSS4_4Day_4_DSS
SA331578WT_DSS4_8Day_4_DSS
SA331579WT_DSS4_1Day_4_DSS
SA331580WT_DSS4_9Day_4_DSS
SA331581WT_DSS4_7Day_4_DSS
SA331582WT_DSS4_6Day_4_DSS
SA331583WT_DSS4_5Day_4_DSS
SA331584IL10_KO_HC5Healthy_IL10-/-
SA331585IL10_KO_HC4Healthy_IL10-/-
SA331586IL10_KO_HC3Healthy_IL10-/-
SA331587IL10_KO_HC6Healthy_IL10-/-
SA331588IL10_KO_HC7Healthy_IL10-/-
SA331589IL10_KO_HC9Healthy_IL10-/-
SA331590IL10_KO_HC8Healthy_IL10-/-
SA331591IL10_KO_HC2Healthy_IL10-/-
SA331592IL10_KO_HC10Healthy_IL10-/-
SA331593IL10_KO_HC1Healthy_IL10-/-
SA331594IL10_KO_ILL6Ill_IL10-/-
SA331595IL10_KO_ILL7Ill_IL10-/-
SA331596IL10_KO_ILL8Ill_IL10-/-
SA331597IL10_KO_ILL10Ill_IL10-/-
SA331598IL10_KO_ILL9Ill_IL10-/-
SA331599IL10_KO_ILL2Ill_IL10-/-
SA331600IL10_KO_ILL3Ill_IL10-/-
SA331601IL10_KO_ILL4Ill_IL10-/-
SA331602IL10_KO_ILL5Ill_IL10-/-
SA331603IL10_KO_ILL1Ill_IL10-/-
SA331604WT_HC_5WT
SA331605WT_HC_2WT
SA331606WT_HC_10WT
SA331607WT_HC_1WT
SA331608WT_HC_3WT
SA331609WT_HC_4WT
SA331610WT_HC_8WT
SA331611WT_HC_7WT
SA331612WT_HC_6WT
SA331613WT_HC_9WT
Showing results 1 to 50 of 50

Collection:

Collection ID:CO003162
Collection Summary:Colons were harvested from euthanized mice and flash-frozen in liquid nitrogen. For all downstream analyses, the distal region of the colon (0.5-2 cm from rectum) was used, since it is where colitis is most pronounced in these models.
Sample Type:Colon
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003178
Treatment Summary:Acute colitis was induced in wild type (WT) C57BL/6 mice via addition of 1.25% DSS into the drinking water for seven days. To gain insight on chronic intestinal inflammation, we used C57BL/6 IL-10-/- mice that spontaneously develop chronic colon inflammation. This inflammation is not chemically induced, but rather is considered to be a result of a dysregulated immune system, which more resembles the clinical manifestation of chronic UC and CD patients and mimics a monogenic form of IBD20. In order to synchronize and accelerate the onset of chronic colitis, mice were exposed to 200 ppm piroxicam (Sigma-Aldrich ltd.) via supplementation in normal murine chow for 14 days. With the described experimental procedures, we obtained five groups of mice (10 mice per group) for further analysis: 1) Healthy WT; 2) Day 4 of DSS (pre-symptomatic); 3) Day 10 of DSS (acute colitis); 4) Healthy IL-10-/- (pre-symptomatic); and 5) Ill IL-10-/- (chronic colitis).

Sample Preparation:

Sampleprep ID:SP003175
Sampleprep Summary:Frozen colon samples were trimmed (15–20 mg) to fit HR-MAS ZrO2 rotor insert capacity (50 μL). Each insert was filled with 2H2O containing 5.8 mM sodium trimethylsilyl [2,2,3,3-2H4]propionate (TMSP). Inserts were covered with plug and plug-restraining screw and inserted into the 4 mm rotor for HR-MAS probe.

Analysis:

Analysis ID:AN005008
Analysis Type:NMR
Num Factors:5
Num Metabolites:22
Units:AU

NMR:

NMR ID:NM000274
Analysis ID:AN005008
Instrument Name:Bruker 600 MHz
Instrument Type:FT-NMR
NMR Experiment Type:1D-1H
Spectrometer Frequency:600 MHz
NMR Probe:HR-MAS TXI 1H/13C/15N probe
NMR Solvent:H2O
NMR Tube Size:4 mm rotor for HR-MAS probe
Pulse Sequence:CPMG
Water Suppression:water peak suppression-presaturation
Temperature:277 K
Number Of Scans:64
Dummy Scans:4
Acquisition Time:1.36s
Spectral Width:12 KHz
Num Data Points Acquired:32 k
Line Broadening:1
Baseline Correction Method:automatic
Chemical Shift Ref Std:doublet at 5.24 ppm
Binned Increment:0.02 ppm
Binned Data Excluded Range:4.5-5.5 ppm
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